Phenotypes associated with this allele

• Allele Symbol: Tg(Stra8-icre)1Reb
• Allele Name: transgene insertion 1, Robert E Braun
• Allele ID: MGI:3779079
• Summary: 56 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	G3bp2^em1Smoc/G3bp2^em1.1Smoc Tg(Stra8-icre)1Reb/0	B6.Cg-G3bp2^em1Smoc/G3bp2^em1.1Smoc Tg(Stra8-icre)1Reb	MGI:7333229
cn2	Hells^tm1c(EUCOMM)Wtsi/Hells^tm1d(EUCOMM)Wtsi Tg(Stra8-icre)1Reb/0	(B6(Cg)-Hells^tm1c(EUCOMM)Wtsi/BakrJ x B6.Cg-Hells^tm1d(EUCOMM)Wtsi Tg(Stra8-icre)1Reb/Bakr)F1	MGI:6389564
cn3	Upf3a^tm1.1Wilk/Upf3a^tm1.1Wilk Tg(Stra8-icre)1Reb/0	involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ	MGI:6117761
cn4	Ift172^tm1.1Rama/Ift172^tm1.1Rama Tg(Stra8-icre)1Reb/0	involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ	MGI:6860531
cn5	Tg(Stra8-icre)1Reb/0 Upf3a^tm1.1Wilk/Upf3a^+	involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ	MGI:6117762
cn6	Golga2^tm1.1Baos/Golga2^tm1.2Baos Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6 * FVB/NJ	MGI:6885893
cn7	Cdk1^tm3Kald/Cdk1^+ Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6 * FVB/NJ	MGI:6201526
cn8	Aldh1a1^tm1Gdu/Aldh1a1^tm1Gdu Aldh1a2^tm1.1Mbp/Aldh1a2^tm1.2Mbp Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6 * FVB/NJ	MGI:7327642
cn9	Cops5^tm1Rpar/Cops5^tm1Rpar Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6 * FVB/NJ * SJL	MGI:6858076
cn10	Fbxo43^tm1.1Kald/Fbxo43^tm1.1Kald Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6 * FVB/NJ * SJL	MGI:6201523
cn11	Mfn1^tm2Dcc/Mfn1^tm2Dcc Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6J * FVB/NJ	MGI:7448527
cn12	Carm1^tm1.1Mtb/Carm1^tm1.1Mtb Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6J * FVB/NJ	MGI:6283447
cn13	Mfn1^tm2Dcc/Mfn1^tm2Dcc Mfn2^tm3Dcc/Mfn2^tm3Dcc Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6J * FVB/NJ	MGI:7448532
cn14	Mfn2^tm3Dcc/Mfn2^tm3Dcc Tg(Stra8-icre)1Reb/0	involves: 129 * C57BL/6J * FVB/NJ	MGI:7448528
cn15	Rhox^tm1Wilk/Rhox^tm1Wilk Tg(RNU6-RNAi:Rhox3)2Wilk/0 Tg(Stra8-icre)1Reb/0	involves: 129 * FVB/NJ	MGI:5763277
cn16	Piwil2^tm1.1Doca/Piwil2^tm2.1Doca Tg(Stra8-icre)1Reb/0	involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * FVB/NJ	MGI:5521299
cn17	Piwil2^tm2.1Doca/Piwil2^tm2.1Doca Tg(Stra8-icre)1Reb/0	involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * FVB/NJ	MGI:5521297
cn18	Kdm6b^tm1.1Iwam/Kdm6b^tm1.2Iwam Tg(Stra8-icre)1Reb/0	involves: 129P2/OlaHsd * C57BL/6J * FVB/NJ	MGI:5551619
cn19	Mgat1^tm2Jxm/Mgat1^tm2Jxm Tg(Stra8-icre)1Reb/0	involves: 129S1/Sv * 129X1/SvJ * FVB/NJ	MGI:6888114
cn20	Agbl5^tm1.1Ics/Agbl5^tm1.1Ics Tg(Stra8-icre)1Reb/0	involves: 129S2/SvPas * C57BL/6N	MGI:6887929
cn21	Csnk2b^tm1.1Bb/Csnk2b^tm1.2Bb Tg(Stra8-icre)1Reb/0	involves: 129S2/SvPasCrl * C57BL/6 * FVB/NJ	MGI:6845052
cn22	Ift27^tm1c(EUCOMM)Hmgu/Ift27^tm1c(EUCOMM)Hmgu Tg(Stra8-icre)1Reb/0	involves: 129S4/SvJae * C57BL/6J * C57BL/6N * FVB/NJ	MGI:6861833
cn23	Ift20^tm1.1Gjp/Ift20^tm1.2Gjp Tg(Stra8-icre)1Reb/0	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * FVB/NJ	MGI:6865740
cn24	Mettl3^tm1.1Jhha/Mettl3^tm1.1Jhha Tg(Stra8-icre)1Reb/0	involves: 129S4/SvJaeSor * BALB/c * C57BL/6 * FVB/NJ	MGI:6491901
cn25	Ift74^tm1c(EUCOMM)Hmgu/Ift74^tm1c(EUCOMM)Hmgu Tg(Stra8-icre)1Reb/0	involves: 129S4/SvJaeSor * C57BL/6N * FVB/NJ	MGI:6864146
cn26	Fis1^tm1Dcc/Fis1^tm1.1Dcc Gt(ROSA)26Sor^tm1.1(CAG-COX8A/Dendra2)Dcc/Gt(ROSA)26Sor^+ Tg(Stra8-icre)1Reb/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/NJ	MGI:6755500
cn27	Huwe1^tm1Alas/Y Tg(Stra8-icre)1Reb/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB/NJ	MGI:7286183
cn28	Rxfp2^tm1Aia/Rxfp2^tm1c(EUCOMM)Wtsi Tg(Stra8-icre)1Reb/0	involves: 129S7/SvEvBrd * C57BL/6N * FVB/NJ	MGI:5473319
cn29	Spata19^tm1Lij/Spata19^tm1Lij Tg(Stra8-icre)1Reb/0	involves: 129S7/SvEvBrd * FVB/NJ	MGI:6510020
cn30	Ppp1cc^tm1Lex/Ppp1cc^tm1Lex Tg(Stra8-icre)1Reb/0	involves: 129S/SvEvBrd * FVB/NJ	MGI:5559510
cn31	Ppp4c^em1Qys/Ppp4c^em1Qys Tg(Stra8-icre)1Reb/0	involves: 129S/SvEv * C57BL/6 * FVB/NJ	MGI:7281440
cn32	Atg5^tm1Myok/Atg5^tm1Myok Tg(Stra8-icre)1Reb/0	involves: 129S/SvEv * FVB/NJ	MGI:6883592
cn33	Rdh10^tm1c(KOMP)Wtsi/Rdh10^tm1c(KOMP)Wtsi Tg(Amh-cre)8815Reb/0 Tg(RARE-Hspa1b/lacZ)12Jrt/0 Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * C57BL/6N * CD-1 * FVB/N * SJL	MGI:5475537
cn34	Ift81^tm1c(EUCOMM)Wtsi/Ift81^tm1c(EUCOMM)Wtsi Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * C57BL/6N * FVB/NJ	MGI:6864067
cn35	Rdh10^tm1c(KOMP)Wtsi/Rdh10^tm1c(KOMP)Wtsi Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * C57BL/6N * FVB/NJ * SJL	MGI:5475535
cn36	Rdh10^tm1c(KOMP)Wtsi/Rdh10^tm1c(KOMP)Wtsi Tg(Amh-cre)8815Reb/0 Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * C57BL/6N * FVB/N * SJL	MGI:5475536
cn37	Racgap1^tm1Mahi/Racgap1^tm1Mahi Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * FVB/NJ	MGI:6864268
cn38	Hnrnpk^tm1.1Cya/Hnrnpk^tm1.1Cya Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * FVB/NJ	MGI:7287839
cn39	Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * FVB/NJ * SJL	MGI:7266812
cn40	Ewsr1^tm1c(EUCOMM)Wtsi/Ewsr1^tm1d(EUCOMM)Wtsi Tg(Stra8-icre)1Reb/0	involves: C57BL/6J	MGI:6830505
cn41	Pramex1^tm1c(KOMP)Wtsi/Y Tg(Stra8-icre)1Reb/0	involves: C57BL/6J * C57BL/6N	MGI:6457270
cn42	Slc9a8^tm1c(KOMP)Wtsi/Slc9a8^tm1c(KOMP)Wtsi Tg(Stra8-icre)1Reb/0	involves: C57BL/6J * C57BL/6N * FVB/NJ	MGI:6887371
cn43	Mfn2^em1Cya/Mfn2^em1Cya Tg(Stra8-icre)1Reb/0	involves: C57BL/6J * FVB/NJ	MGI:7327651
cn44	Ranbp9^tm1Wyan/Ranbp9^tm1Wyan Tg(Stra8-icre)1Reb/0	involves: C57BL/6J * FVB/NJ	MGI:5702983
cn45	Rbm46^em3Rpc/Rbm46^em3Rpc Tg(Stra8-icre)1Reb/0	involves: C57BL/6J * FVB/NJ * SJL/J	MGI:7356612
cn46	Cep250^tm1a(EUCOMM)Wtsi/Cep250^tm1a(EUCOMM)Wtsi Tg(Stra8-icre)1Reb/0	involves: C57BL/6N	MGI:7444373
cn47	Katnal2^tm1c(EUCOMM)Wtsi/Katnal2^tm1c(EUCOMM)Wtsi Tg(Stra8-icre)1Reb/0	involves: C57BL/6N * FVB/NJ	MGI:6274241
cn48	Tdrd5^tm1c(EUCOMM)Hmgu/Tdrd5^tm1c(EUCOMM)Hmgu Tg(Stra8-icre)1Reb/0	involves: C57BL/6N * FVB/NJ	MGI:6156877
cn49	Crisp2^tm1c(KOMP)Mbp/Crisp2^tm1c(KOMP)Mbp Tg(Stra8-icre)1Reb/0	involves: C57BL/6N * FVB/NJ	MGI:6369095
cn50	Phf7^tm1c(EUCOMM)Hmgu/Phf7^tm1c(EUCOMM)Hmgu Tg(Stra8-icre)1Reb/0	involves: C57BL/6N * FVB/NJ	MGI:6690603
cn51	Ift140^tm1c(KOMP)Wtsi/Ift140^tm1c(KOMP)Wtsi Tg(Stra8-icre)1Reb/0	involves: C57BL/6N * FVB/NJ	MGI:6857985
cn52	Cenpv^tm1c(EUCOMM)Hmgu/Cenpv^tm1c(EUCOMM)Hmgu Tg(Stra8-icre)1Reb/0	involves: C57BL/6N * FVB/NJ	MGI:6838391
cn53	Tg(Stra8-icre)1Reb/0 Zscan21^tm1.1Jiwa/Zscan21^tm1.1Jiwa	involves: FVB/NJ	MGI:5904161
cn54	Tg(RNU6-RNAi:Rhox3)2Wilk/0 Tg(Stra8-icre)1Reb/0	involves: FVB/NJ	MGI:5763275
cn55	Cxxc1^tm2.1Skk/Cxxc1^tm2.1Skk Tg(Stra8-icre)1Reb/0	involves: FVB/NJ	MGI:7507026
tg56	Tg(Stra8-icre)1Reb/0	involves: FVB	MGI:3850155

Genotype
MGI:7333229

cn1

• Allelic Composition: G3bp2^em1Smoc/G3bp2^em1.1Smoc; Tg(Stra8-icre)1Reb/0
• Genetic Background: B6.Cg-G3bp2^em1Smoc/G3bp2^em1.1Smoc Tg(Stra8-icre)1Reb

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

reproductive system

reproductive system phenotype ( J:327036 )

♂ • male mice exhibit normal spermatogenesis and fertility

increased male germ cell apoptosis ( J:327036 )

♂

cellular

increased male germ cell apoptosis ( J:327036 )

♂

Genotype
MGI:6389564

cn2

• Allelic Composition: Hells^{tm1c(EUCOMM)Wtsi}/Hells^{tm1d(EUCOMM)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: (B6(Cg)-Hells^{tm1c(EUCOMM)Wtsi}/BakrJ x B6.Cg-Hells^{tm1d(EUCOMM)Wtsi} Tg(Stra8-icre)1Reb/Bakr)F1

cellular

decreased male germ cell number ( J:283594 )

♂

abnormal meiosis ( J:283594 )

♂ • Incomplete DNA repair at double stranded breaks in pachytene spermatocytes and the genomic locations of the double stranded breaks is abnormal

arrest of male meiosis ( J:283594 )

♂ • arrest at the late-zygotene to early pachytene stage, with an increased proportion of leptotene and zygotene and absence of normal pachytene and diplotene spermatocytes, with the pachytene cells having H2AX phosphorylation and incomplete synapsis

increased male germ cell apoptosis ( J:283594 )

♂

abnormal DNA methylation ( J:283594 )

♂

abnormal DNA methylation during gametogenesis ( J:283594 )

♂ • At 12 days of age spermatocytes show a decrease in epigenomic modification at recombination hotspots, H3K4me3 and chromatin accessibility sites at recombination hotspots are decreased

endocrine/exocrine glands

decreased testis weight ( J:283594 )

♂

reproductive system

decreased male germ cell number ( J:283594 )

♂

abnormal meiosis ( J:283594 )

♂ • Incomplete DNA repair at double stranded breaks in pachytene spermatocytes and the genomic locations of the double stranded breaks is abnormal

arrest of male meiosis ( J:283594 )

♂ • arrest at the late-zygotene to early pachytene stage, with an increased proportion of leptotene and zygotene and absence of normal pachytene and diplotene spermatocytes, with the pachytene cells having H2AX phosphorylation and incomplete synapsis

increased male germ cell apoptosis ( J:283594 )

♂

abnormal DNA methylation during gametogenesis ( J:283594 )

♂ • At 12 days of age spermatocytes show a decrease in epigenomic modification at recombination hotspots, H3K4me3 and chromatin accessibility sites at recombination hotspots are decreased

decreased testis weight ( J:283594 )

♂

male infertility ( J:283594 )

♂ • these males fail to sire offspring

Genotype
MGI:6117761

cn3

• Allelic Composition: Upf3a^tm1.1Wilk/Upf3a^tm1.1Wilk; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ

cellular

cellular phenotype ( J:234504 )

♂N • number of apoptotic testicular cells at age 1 and 2 weeks

abnormal spermatid morphology ( J:234504 )

♂ • reduced number of cells expressing spermatid-specific markers Tp2 and Prm2 amongst dissociated cells from purified seminiferous tubules

♂ • reduced fraction of seminiferous tubules containing elongating spermatids

abnormal spermatocyte morphology ( J:234504 )

♂ • 6-fold fewer pachytene spermatocytes compared to wild-type

♂ • significant reduction in pachytene spermatocytes amongst dissociated cells from purified seminiferous tubules

♂ • reduced number of cells expressing spermatocyte-specific markers Spo11 and Sycp3 amongst dissociated cells from purified seminiferous tubules

♂ • reduced number of cells expressing spermatocyte-specific markers Stra8, Spo11 and Sycp3 amongst FACS sorted 4N spermatocytes

abnormal spermatogonia morphology ( J:234504 )

♂ • reduced number of cells expressing germ cell marker Ldhc amongst dissociated cells from purified seminiferous tubules

decreased male germ cell number ( J:234504 )

♂ • around 6-fold fewer round and elongated spermatids than wild-type

♂ • 6-fold fewer pachytene spermatocytes compared to wild-type

♂ • significant reduction in pachytene spermatocytes amongst dissociated cells from purified seminiferous tubules

♂ • reduced fraction of seminiferous tubules containing elongating spermatids

♂ • reduced number of cells expressing Ldhc (germ cell marker), Spo11 and Sycp3 (spermatocyte-specific markers), and Tp2 and Prm2 (spermatid-specific markers) amongst dissociated cells from purified seminiferous tubules

♂ • normal number of leptotene/zygotene spermatocytes

♂ • normal number of spermatogonia at age 1 and 2 weeks

♂ • normal number of apoptotic testicular cells at age 1 and 2 weeks

oligozoospermia ( J:234504 )

♂ • sperm count reduced 10-fold to around 10% of wild-type

abnormal cell physiology ( J:234504 )

♂ • reduced expression of NMD (nonsense-mediated decay) target transcripts Atf4, Cdh11, Ern2, Smad5 and Smad7 in FACS sorted spermatocytes from 4-week old mice

abnormal male meiosis ( J:234504 )

♂ • significant reduction in pachytene spermatocytes amongst dissociated cells from purified seminiferous tubules

♂ • 6-fold fewer pachytene spermatocytes compared to wild-type

increased male germ cell apoptosis ( J:234504 )

♂ • around 3-fold increase in apoptotic male germ cells per tubule at age 4 weeks

growth/size/body

growth/size/body region phenotype ( J:234504 )

N • body weight and overall morphology

reproductive system

abnormal spermatid morphology ( J:234504 )

♂ • reduced number of cells expressing spermatid-specific markers Tp2 and Prm2 amongst dissociated cells from purified seminiferous tubules

♂ • reduced fraction of seminiferous tubules containing elongating spermatids

abnormal spermatocyte morphology ( J:234504 )

♂ • 6-fold fewer pachytene spermatocytes compared to wild-type

♂ • significant reduction in pachytene spermatocytes amongst dissociated cells from purified seminiferous tubules

♂ • reduced number of cells expressing spermatocyte-specific markers Spo11 and Sycp3 amongst dissociated cells from purified seminiferous tubules

♂ • reduced number of cells expressing spermatocyte-specific markers Stra8, Spo11 and Sycp3 amongst FACS sorted 4N spermatocytes

abnormal spermatogonia morphology ( J:234504 )

♂ • reduced number of cells expressing germ cell marker Ldhc amongst dissociated cells from purified seminiferous tubules

decreased male germ cell number ( J:234504 )

♂ • around 6-fold fewer round and elongated spermatids than wild-type

♂ • 6-fold fewer pachytene spermatocytes compared to wild-type

♂ • significant reduction in pachytene spermatocytes amongst dissociated cells from purified seminiferous tubules

♂ • reduced fraction of seminiferous tubules containing elongating spermatids

♂ • reduced number of cells expressing Ldhc (germ cell marker), Spo11 and Sycp3 (spermatocyte-specific markers), and Tp2 and Prm2 (spermatid-specific markers) amongst dissociated cells from purified seminiferous tubules

♂ • normal number of leptotene/zygotene spermatocytes

♂ • normal number of spermatogonia at age 1 and 2 weeks

♂ • normal number of apoptotic testicular cells at age 1 and 2 weeks

oligozoospermia ( J:234504 )

♂ • sperm count reduced 10-fold to around 10% of wild-type

abnormal male meiosis ( J:234504 )

♂ • significant reduction in pachytene spermatocytes amongst dissociated cells from purified seminiferous tubules

♂ • 6-fold fewer pachytene spermatocytes compared to wild-type

increased male germ cell apoptosis ( J:234504 )

♂ • around 3-fold increase in apoptotic male germ cells per tubule at age 4 weeks

Genotype
MGI:6860531

cn4

• Allelic Composition: Ift172^tm1.1Rama/Ift172^tm1.1Rama; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ

reproductive system

oligozoospermia ( J:302808 )

♂ • number of sperm collected from the cauda epididymis is significantly reduced

teratozoospermia ( J:302808 )

♂ • >80% of total sperm exhibit morphological abnormalities

abnormal sperm flagellum morphology ( J:302808 )

♂ • some sperm exhibit vacuoles in the flagellum

abnormal outer dense fiber morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits in the midpiece

abnormal sperm axoneme morphology ( J:302808 )

♂ • some epididymal sperm display abnormal core axonemes and accessory structures, including missing or disorganized 9 + 2 arrangement of the microtubules

abnormal sperm midpiece morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits

♂ • failure of mitochondria and ODFs to assemble properly into the flagellum is also observed

♂ • however, the fibrous sheath structure appears normal

kinked sperm flagellum ( J:302808 )

♂ • most epididymal spermatozoa show bent flagella at the midpiece

abnormal sperm head morphology ( J:302808 )

♂ • elongating spermatids exhibit abnormal head formation/shapes

abnormal acrosome morphology ( J:302808 )

♂ • localization of an acrosome marker (Sp56) is normal in round spermatids but appears to be abnormal in some elongating spermatids

♂ • elongating spermatids with misshapen heads also show distorted acrosomes, suggesting that this might be a secondary effect

abnormal spermatid morphology ( J:302808 )

♂ • elongating spermatids exhibit a mislocalized and longer manchette; those with abnormally developed heads also show distorted acrosomes

ectopic manchette ( J:302808 )

♂ • manchette is mislocalized in testicular germ cells

elongated manchette ( J:302808 )

♂ • isolated testicular germ cells exhibit a longer manchette than control cells

abnormal seminiferous tubule morphology ( J:302808 )

♂ • seminiferous tubules have very small lumens and contain only few spermatid tails in the spermiogenesis phase

small seminiferous tubules ( J:302808 )

♂

abnormal spermiogenesis ( J:302808 )

♂ • cauda epididymis shows a low concentration of sperm in the lumen, with non-aligned sperm and numerous abnormalities

♂ • abnormal sperm heads and tails are observed, along with sloughed round bodies of residual spermatid cytoplasm; an occasional sloughed spermatocyte nucleus is observed

abnormal spermiation ( J:302808 )

♂ • fewer sperm are detected in the lumen of seminiferous tubules in the spermiogenesis phase

abnormal cauda epididymis morphology ( J:302808 )

♂ • fewer sperm are present in the cauda epididymal lumen and round bodies and cytoplasmic debris are also present

decreased litter size ( J:302808 )

♂ • males produce significantly fewer pups per litter than control males (4.57 +/- 2.5 versus 8.67 +/- 1.2, respectively)

reduced male fertility ( J:302808 )

♂ • after mating with wild-type females of known fertility for over 2 months, less than 50% of adult males are fertile and produce offspring with decreased litter sizes

♂ • however, testis/body weight ratio is similar to that in control males

abnormal sperm physiology ( J:302808 )

♂ • expression levels of ODF2 (a component of the outer dense fiber), AKAP4 (a component of fibrous sheath), and two IFT components IFT25 and IFT57 are dramatically reduced in epididymal sperm

asthenozoospermia ( J:302808 )

♂ • sperm motility measured as curvilinear velocity (VCL) is significantly decreased

cellular

oligozoospermia ( J:302808 )

♂ • number of sperm collected from the cauda epididymis is significantly reduced

teratozoospermia ( J:302808 )

♂ • >80% of total sperm exhibit morphological abnormalities

abnormal sperm flagellum morphology ( J:302808 )

♂ • some sperm exhibit vacuoles in the flagellum

abnormal outer dense fiber morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits in the midpiece

abnormal sperm axoneme morphology ( J:302808 )

♂ • some epididymal sperm display abnormal core axonemes and accessory structures, including missing or disorganized 9 + 2 arrangement of the microtubules

abnormal sperm midpiece morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits

♂ • failure of mitochondria and ODFs to assemble properly into the flagellum is also observed

♂ • however, the fibrous sheath structure appears normal

kinked sperm flagellum ( J:302808 )

♂ • most epididymal spermatozoa show bent flagella at the midpiece

abnormal sperm head morphology ( J:302808 )

♂ • elongating spermatids exhibit abnormal head formation/shapes

abnormal acrosome morphology ( J:302808 )

♂ • localization of an acrosome marker (Sp56) is normal in round spermatids but appears to be abnormal in some elongating spermatids

♂ • elongating spermatids with misshapen heads also show distorted acrosomes, suggesting that this might be a secondary effect

abnormal spermatid morphology ( J:302808 )

♂ • elongating spermatids exhibit a mislocalized and longer manchette; those with abnormally developed heads also show distorted acrosomes

ectopic manchette ( J:302808 )

♂ • manchette is mislocalized in testicular germ cells

elongated manchette ( J:302808 )

♂ • isolated testicular germ cells exhibit a longer manchette than control cells

abnormal centrosome morphology ( J:302808 )

♂ • immunofluorescence staining of gamma-tubulin (a centrosome marker) showed that ~22.5% of isolated male germ cells exhibit multiple centrosomal signals versus less than 1% in control cells, suggesting centrosome fragmentation

asthenozoospermia ( J:302808 )

♂ • sperm motility measured as curvilinear velocity (VCL) is significantly decreased

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:302808 )

♂ • seminiferous tubules have very small lumens and contain only few spermatid tails in the spermiogenesis phase

small seminiferous tubules ( J:302808 )

♂

Genotype
MGI:6117762

cn5

• Allelic Composition: Tg(Stra8-icre)1Reb/0; Upf3a^tm1.1Wilk/Upf3a⁺
• Genetic Background: involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ

cellular

abnormal spermatocyte morphology ( J:234504 )

♂ • reduced number of pachytene spermatocytes amongst FACS sorted cells at age 4 weeks

♂ • reduced number of cells expressing spermatocyte-specific markers amongst purified spermatocytes

decreased male germ cell number ( J:234504 )

♂ • reduced number of pachytene spermatocytes and postmeiotic germ cells amongst FACS sorted cells at age 4 weeks

♂ • reduced number of cells expressing spermatocyte-specific markers amongst purified spermatocytes

♂ • reduced number of cells expressing spermatogenic markers at age 4 weeks

reproductive system

abnormal spermatocyte morphology ( J:234504 )

♂ • reduced number of pachytene spermatocytes amongst FACS sorted cells at age 4 weeks

♂ • reduced number of cells expressing spermatocyte-specific markers amongst purified spermatocytes

decreased male germ cell number ( J:234504 )

♂ • reduced number of pachytene spermatocytes and postmeiotic germ cells amongst FACS sorted cells at age 4 weeks

♂ • reduced number of cells expressing spermatocyte-specific markers amongst purified spermatocytes

♂ • reduced number of cells expressing spermatogenic markers at age 4 weeks

Genotype
MGI:6885893

cn6

• Allelic Composition: Golga2^tm1.1Baos/Golga2^tm1.2Baos; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/NJ

cellular

abnormal sperm mitochondrial sheath morphology ( J:273740 )

♂ • Mitotracker-positive mitochondria are abnormally found in the sperm head surrounding the deformed nucleus instead of the flagellar midpiece, suggesting improper mitochondrial sheath assembly

absent sperm mitochondrial sheath ( J:273740 )

♂ • Mitotracker staining revealed complete absence of the mitochondrial sheath in the midpiece of sperm tails

abnormal sperm head morphology ( J:273740 )

♂ • Mitotracker-positive mitochondria are abnormally found in the sperm head surrounding the nucleus

globozoospermia ( J:273740 )

♂ • at 2 months of age, sperm heads in the cauda epididymides are round

absent acrosome ( J:273740 )

♂ • acrosome is absent, as shown by the absence of Afaf signal in most germ cells and of acrosome-specific protein ZP3R (aka SP56) in sperm

abnormal sperm nucleus morphology ( J:273740 )

♂

reproductive system

abnormal sperm mitochondrial sheath morphology ( J:273740 )

♂ • Mitotracker-positive mitochondria are abnormally found in the sperm head surrounding the deformed nucleus instead of the flagellar midpiece, suggesting improper mitochondrial sheath assembly

absent sperm mitochondrial sheath ( J:273740 )

♂ • Mitotracker staining revealed complete absence of the mitochondrial sheath in the midpiece of sperm tails

abnormal sperm head morphology ( J:273740 )

♂ • Mitotracker-positive mitochondria are abnormally found in the sperm head surrounding the nucleus

globozoospermia ( J:273740 )

♂ • at 2 months of age, sperm heads in the cauda epididymides are round

absent acrosome ( J:273740 )

♂ • acrosome is absent, as shown by the absence of Afaf signal in most germ cells and of acrosome-specific protein ZP3R (aka SP56) in sperm

abnormal sperm nucleus morphology ( J:273740 )

♂

abnormal spermiogenesis ( J:273740 )

♂ • defects in spermiogenesis are observed at 2 months of age

♂ • however, seminiferous tubule morphology is grossly normal

male infertility ( J:273740 )

♂

Genotype
MGI:6201526

cn7

• Allelic Composition: Cdk1^tm3Kald/Cdk1⁺; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/NJ

reproductive system

azoospermia ( J:251984 )

♂ • tubules contain only Sertoli cells with only rare spermatogonia

arrest of male meiosis ( J:251984 )

♂ • early

small testis ( J:251984 )

♂

endocrine/exocrine glands

small testis ( J:251984 )

♂

cellular

azoospermia ( J:251984 )

♂ • tubules contain only Sertoli cells with only rare spermatogonia

arrest of male meiosis ( J:251984 )

♂ • early

Genotype
MGI:7327642

cn8

• Allelic Composition: Aldh1a1^tm1Gdu/Aldh1a1^tm1Gdu; Aldh1a2^tm1.1Mbp/Aldh1a2^tm1.2Mbp; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/NJ

reproductive system

reproductive system phenotype ( J:324715 )

♂N • male mice exhibit normal spermatogenesis

Genotype
MGI:6858076

cn9

• Allelic Composition: Cops5^tm1Rpar/Cops5^tm1Rpar; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/NJ * SJL

reproductive system

increased male germ cell apoptosis ( J:307573 )

♂ • TUNEL staining revealed a dramatic increase in the presence of apoptotic germ cells in the seminiferous tubules

♂ • Western blot analysis showed that PARP1 and FANK1 expression levels are dramatically reduced, whereas Caspase-3 expression level is significantly increased

asthenozoospermia ( J:307573 )

♂ • less than 10% of sperm are motile; however, their curvilinear velocity is significantly reduced

immotile sperm ( J:307573 )

♂ • most sperm display no mobility

abnormal seminiferous tubule morphology ( J:307573 )

♂ • seminiferous tubule structure is totally disrupted

abnormal seminiferous tubule epithelium morphology ( J:307573 )

♂ • large vacuoles are present in the epithelium and these are likely the spaces remaining after Sertoli cell phagocytosis of apoptotic cells

abnormal ectoplasmic specialization morphology ( J:307573 )

♂

small testis ( J:307573 )

♂ • adult testis size is markedly reduced

decreased testis weight ( J:307573 )

♂ • testis weight and testis weight/body weight are reduced to about one third of controls

abnormal spermatogenesis ( J:307573 )

♂ • spermatogenesis is severely impaired: a number of degenerating germ cells are observed in the lumen of the seminiferous epithelium, with very few developed elongated spermatids

♂ • round bodies (possibly sloughed germ cells) and cellular debris are seen in the cauda epididymis lumen

oligozoospermia ( J:307573 )

♂ • cauda epididymal sperm counts are severely reduced

teratozoospermia ( J:307573 )

♂ • >80% of sperm exhibit abnormal morphology

abnormal acrosome assembly ( J:307573 )

♂ • few surviving spermatids exhibit little to no staining with acrosome marker peanut-lectin (PNA) while expression level of SPACA1 (another acrosomal component) is significantly reduced

♂ • testicular IFT20 expression level is significantly reduced; although IFT20 is still found in the Golgi apparatus of spermatocytes, it is no longer localized in the acrosome of round spermatids and, instead, it is present as individual vesicles in the cytoplasm

♂ • acrosome formation is absent in most round spermatids; in other spermatids, an abnormal acrosome is formed, or a very thin acrosome is attached to the Sertoli cell membrane by an abnormal ectoplasmic specialization

abnormal sperm nucleus morphology ( J:307573 )

♂ • few germ cells that develop into elongating spermatids exhibit abnormal nuclear structures

abnormal spermatid morphology ( J:307573 )

♂ • elongating spermatids are rarely observed

♂ • few germ cells that develop into elongating spermatids exhibit abnormal nuclei

male infertility ( J:307573 )

♂ • when bred with adult wild-type females of known fertility, none of the 6-wk-old or adult males tested sired any pups/litters during a 2-month breeding period, indicating complete male sterility

♂ • however, mating behavior and vaginal plug formation are normal

cellular

oligozoospermia ( J:307573 )

♂ • cauda epididymal sperm counts are severely reduced

teratozoospermia ( J:307573 )

♂ • >80% of sperm exhibit abnormal morphology

abnormal acrosome assembly ( J:307573 )

♂ • few surviving spermatids exhibit little to no staining with acrosome marker peanut-lectin (PNA) while expression level of SPACA1 (another acrosomal component) is significantly reduced

♂ • testicular IFT20 expression level is significantly reduced; although IFT20 is still found in the Golgi apparatus of spermatocytes, it is no longer localized in the acrosome of round spermatids and, instead, it is present as individual vesicles in the cytoplasm

♂ • acrosome formation is absent in most round spermatids; in other spermatids, an abnormal acrosome is formed, or a very thin acrosome is attached to the Sertoli cell membrane by an abnormal ectoplasmic specialization

abnormal sperm nucleus morphology ( J:307573 )

♂ • few germ cells that develop into elongating spermatids exhibit abnormal nuclear structures

abnormal spermatid morphology ( J:307573 )

♂ • elongating spermatids are rarely observed

♂ • few germ cells that develop into elongating spermatids exhibit abnormal nuclei

increased male germ cell apoptosis ( J:307573 )

♂ • TUNEL staining revealed a dramatic increase in the presence of apoptotic germ cells in the seminiferous tubules

♂ • Western blot analysis showed that PARP1 and FANK1 expression levels are dramatically reduced, whereas Caspase-3 expression level is significantly increased

asthenozoospermia ( J:307573 )

♂ • less than 10% of sperm are motile; however, their curvilinear velocity is significantly reduced

immotile sperm ( J:307573 )

♂ • most sperm display no mobility

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:307573 )

♂ • seminiferous tubule structure is totally disrupted

abnormal seminiferous tubule epithelium morphology ( J:307573 )

♂ • large vacuoles are present in the epithelium and these are likely the spaces remaining after Sertoli cell phagocytosis of apoptotic cells

abnormal ectoplasmic specialization morphology ( J:307573 )

♂

small testis ( J:307573 )

♂ • adult testis size is markedly reduced

decreased testis weight ( J:307573 )

♂ • testis weight and testis weight/body weight are reduced to about one third of controls

Genotype
MGI:6201523

cn10

• Allelic Composition: Fbxo43^tm1.1Kald/Fbxo43^tm1.1Kald; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/NJ * SJL

reproductive system

arrest of male meiosis ( J:251984 )

♂ • in prophase in meiosis I

increased male germ cell apoptosis ( J:251984 )

♂ • at stage XII (pachytene/diplotene)

male infertility ( J:251984 )

♂

cellular

arrest of male meiosis ( J:251984 )

♂ • in prophase in meiosis I

increased male germ cell apoptosis ( J:251984 )

♂ • at stage XII (pachytene/diplotene)

Genotype
MGI:7448527

cn11

• Allelic Composition: Mfn1^tm2Dcc/Mfn1^tm2Dcc; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/NJ

reproductive system

abnormal male germ cell morphology ( J:305430 )

♂ • TEM analysis of adult testes showed mitochondrial swelling and fragmentation in male germ cells

abnormal male germ cell physiology ( J:305430 )

♂ • male germ cells exhibit increased mitochondrial fission

seminiferous tubule degeneration ( J:305430 )

♂ • seminiferous tubules exhibit severe vacuolization defects as early as P28

small testis ( J:305430 )

♂ • adult testis size is grossly smaller than that in controls

decreased testis weight ( J:305430 )

♂ • testis weight/body weight ratio is significantly decreased from P25 to P180

abnormal spermatogenesis ( J:305430 )

♂

oligozoospermia ( J:305430 )

♂

small epididymis ( J:305430 )

♂ • adult epididymis size is grossly smaller than that in controls

male infertility ( J:305430 )

♂

cellular

cellular phenotype ( J:305430 )

♂N • immunofluorescent images of ATP5A (an outer mitochondria membrane marker) showed normal mitochondrial distribution in testicular sections at P25

♂N • calreticulin -- a mitochondria-associated ER membranes (MAMs) and ER marker protein -- does not exhibit any abnormally diffused signal pattern in spermatocytes

abnormal male germ cell morphology ( J:305430 )

♂ • TEM analysis of adult testes showed mitochondrial swelling and fragmentation in male germ cells

oligozoospermia ( J:305430 )

♂

abnormal mitochondrial morphology ( J:305430 )

♂ • TEM analysis of adult testes showed mitochondrial swelling and fragmentation in male germ cells

increased mitochondrial DNA content ( J:305430 )

♂ • adult testes show a significant increase in mitochondrial DNA copy number at P60

abnormal mitochondrial ATP synthesis coupled electron transport ( J:305430 )

♂ • cytochrome c oxidase (COX, complex IV) activity is increased in adult testis sections

♂ • in contrast, succinate dehydrogenase (SDH, complex II) activity is normal

abnormal male germ cell physiology ( J:305430 )

♂ • male germ cells exhibit increased mitochondrial fission

increased mitochondrial fission ( J:305430 )

♂ • male germ cells exhibit increased mitochondrial fission

endocrine/exocrine glands

seminiferous tubule degeneration ( J:305430 )

♂ • seminiferous tubules exhibit severe vacuolization defects as early as P28

small testis ( J:305430 )

♂ • adult testis size is grossly smaller than that in controls

decreased testis weight ( J:305430 )

♂ • testis weight/body weight ratio is significantly decreased from P25 to P180

Genotype
MGI:6283447

cn12

• Allelic Composition: Carm1^tm1.1Mtb/Carm1^tm1.1Mtb; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/NJ

reproductive system

abnormal sperm midpiece morphology ( J:265753 )

♂ • percentage of sperm with a crooked/bent midpiece is significantly increased

abnormal sperm head morphology ( J:265753 )

♂ • most cauda epididymal sperm exhibit deformed head morphology

absent sperm head ( J:265753 )

♂ • percentage of acephalic/headless sperm is significantly increased

abnormal spermatid morphology ( J:265753 )

♂ • a significant drop in the number of late stage spermatids is observed, starting from step 7

decreased male germ cell number ( J:265753 )

♂ • a significant drop in the number of late stage spermatids is observed, starting from step 7

oligozoospermia ( J:265753 )

♂ • at 6 weeks of age, average sperm count in the cauda epididymis is severely reduced

asthenozoospermia ( J:265753 )

♂ • a dramatic decrease in sperm motility is observed

decreased testis weight ( J:265753 )

♂ • a slight but significant decrease in testis weight is observed at 3 months of age

♂ • however, testis size and weight are normal at 6 weeks of age

abnormal spermiogenesis ( J:265753 )

♂ • development of late stage haploid spermatids is impaired

abnormal cauda epididymis morphology ( J:265753 )

♂ • cauda epididymis shows an accumulation of immature germ cells and aberrant sperm

decreased litter size ( J:265753 )

♂ • subfertile males produced an average of 1.7 pups per litter

male infertility ( J:265753 )

♂ • half of the 2-month-old males examined were completely sterile

reduced male fertility ( J:265753 )

♂ • half of the 2-month-old males examined produced very small litters

cellular

abnormal sperm midpiece morphology ( J:265753 )

♂ • percentage of sperm with a crooked/bent midpiece is significantly increased

abnormal sperm head morphology ( J:265753 )

♂ • most cauda epididymal sperm exhibit deformed head morphology

absent sperm head ( J:265753 )

♂ • percentage of acephalic/headless sperm is significantly increased

abnormal spermatid morphology ( J:265753 )

♂ • a significant drop in the number of late stage spermatids is observed, starting from step 7

decreased male germ cell number ( J:265753 )

♂ • a significant drop in the number of late stage spermatids is observed, starting from step 7

oligozoospermia ( J:265753 )

♂ • at 6 weeks of age, average sperm count in the cauda epididymis is severely reduced

asthenozoospermia ( J:265753 )

♂ • a dramatic decrease in sperm motility is observed

endocrine/exocrine glands

decreased testis weight ( J:265753 )

♂ • a slight but significant decrease in testis weight is observed at 3 months of age

♂ • however, testis size and weight are normal at 6 weeks of age

Genotype
MGI:7448532

cn13

• Allelic Composition: Mfn1^tm2Dcc/Mfn1^tm2Dcc; Mfn2^tm3Dcc/Mfn2^tm3Dcc; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/NJ

reproductive system

decreased male germ cell number ( J:305430 )

♂ • almost no round spermatids are detected in testes at P25

small seminiferous tubules ( J:305430 )

♂ • diameter of seminiferous tubules is significantly decreased at P14, P18, P25 and P60

seminiferous tubule degeneration ( J:305430 )

♂ • adult testes show a significantly higher number of atrophic and vacuolated seminiferous tubules

small testis ( J:305430 )

♂ • adult testis size is much smaller than that in either single conditional knockout

decreased testis weight ( J:305430 )

♂ • adult testis weight/body weight ratio is significantly lower than that in either single conditional knockout

abnormal spermatogenesis ( J:305430 )

♂ • at P25 and P56, double conditional mutant males exhibit much more severe spermatogenic defects than either single conditional knockout

abnormal spermatid morphology ( J:305430 )

♂ • almost no round spermatids are detected in testes at P25

abnormal spermatocyte morphology ( J:305430 )

♂ • at P25, mitochondria are abnormally aggregated to one side of the cytoplasm in spermatocytes, unlike in either single conditional knockout where mitochondria distribution is normal

arrest of male meiosis ( J:305430 )

♂ • males fail to complete meiosis; almost no post-meiotic round spermatids are found at P25

small epididymis ( J:305430 )

♂ • adult epididymis size is much smaller than that in either single conditional knockout

male infertility ( J:305430 )

♂

cellular

abnormal spermatid morphology ( J:305430 )

♂ • almost no round spermatids are detected in testes at P25

abnormal spermatocyte morphology ( J:305430 )

♂ • at P25, mitochondria are abnormally aggregated to one side of the cytoplasm in spermatocytes, unlike in either single conditional knockout where mitochondria distribution is normal

decreased male germ cell number ( J:305430 )

♂ • almost no round spermatids are detected in testes at P25

abnormal mitochondrial morphology ( J:305430 )

♂ • at P25, mitochondria are abnormally aggregated to one side of the cytoplasm in spermatocytes, unlike in either single conditional knockout where mitochondria distribution is normal

arrest of male meiosis ( J:305430 )

♂ • males fail to complete meiosis; almost no post-meiotic round spermatids are found at P25

endocrine/exocrine glands

small seminiferous tubules ( J:305430 )

♂ • diameter of seminiferous tubules is significantly decreased at P14, P18, P25 and P60

seminiferous tubule degeneration ( J:305430 )

♂ • adult testes show a significantly higher number of atrophic and vacuolated seminiferous tubules

small testis ( J:305430 )

♂ • adult testis size is much smaller than that in either single conditional knockout

decreased testis weight ( J:305430 )

♂ • adult testis weight/body weight ratio is significantly lower than that in either single conditional knockout

Genotype
MGI:7448528

cn14

• Allelic Composition: Mfn2^tm3Dcc/Mfn2^tm3Dcc; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/NJ

reproductive system

abnormal male germ cell morphology ( J:305430 )

♂ • at P42, late-stage spermatocytes and round spermatids appear to gradually vacuolize

♂ • TEM analysis of adult testes showed mitochondrial swelling and fragmentation in male germ cells

decreased male germ cell number ( J:305430 )

♂ • at P42, late-stage spermatocytes and round spermatids are decreased in number

oligozoospermia ( J:305430 )

♂ • adult males show a dramatic reduction in the number of spermatozoa retrieved from the cauda epididymis

increased testis apoptosis ( J:305430 )

♂ • TUNEL assays show a significantly increased number of apoptotic cells in the testes at P35 and P56

♂ • however, testis histology is normal at P7-P28 and no increase in apoptosis is noted at P14 and P28

abnormal male germ cell physiology ( J:305430 )

♂ • male germ cells exhibit increased mitochondrial fission

increased male germ cell apoptosis ( J:305430 )

♂ • from P35, most male germ cells are gradually lost by apoptosis

small seminiferous tubules ( J:305430 )

♂ • as adult males age, the number of severely atrophic seminiferous tubules is increased

seminiferous tubule degeneration ( J:305430 )

♂ • as adult males age, seminiferous tubules become severely atrophic and vacuolated (P60 to P120)

small testis ( J:305430 )

♂ • testes are significantly smaller at P56

decreased testis weight ( J:305430 )

♂ • testis weight/body weight ratio is significantly decreased from P35 to P120

abnormal spermatogenesis ( J:305430 )

♂ • males show age-dependent spermatogenic defects, with germ cells starting to decline after P35

teratozoospermia ( J:305430 )

♂ • only ~2% of epididymal sperm display normal morphology versus ~80% in wild-type controls

coiled sperm flagellum ( J:305430 )

♂ • ~14% of sperm exhibit a coiled tail

abnormal sperm head morphology ( J:305430 )

♂ • ~31% of sperm exhibit a bent head

absent sperm head ( J:305430 )

♂ • ~53% of sperm are acephalic

abnormal spermatid morphology ( J:305430 )

♂ • at P42, round spermatids are decreased in number and appear to gradually vacuolize

♂ • analysis of the mitochondrial aspect ratio (AR) distribution (where AR is ratio of the major axis to the minor axis of mitochondria) showed an increased % of short mitochondria in round spermatids

♂ • the distance between mitochondria and endoplasmic reticulum (ER) is increased by ~16% while the % of mitochondria-ER contacts is reduced by almost 50% and the ER-mitochondria contact coefficient (ERMICC) is reduced by >30% in round spermatids

abnormal spermatocyte morphology ( J:305430 )

♂ • at P42, late-stage spermatocytes are decreased in number and appear to gradually vacuolize

♂ • at P60, pachytene spermatocytes show a significantly increased thickness of the inter-mitochondrial cement (IMC)

♂ • at P18, immunostaining of calreticulin -- a mitochondria-associated ER membranes (MAMs) and ER marker protein -- showed a diffused granular pattern in the cytoplasm of spermatocytes instead of the continuous perinuclear localization seen in controls; at P60, calreticulin signals appear to be reduced and show diffused granular distribution

small epididymis ( J:305430 )

♂ • epididymis is significantly smaller at P56

male infertility ( J:305430 )

♂ • all males fail to produce offspring after mating with fertility-proven adult wild-type females for 5 months

cellular

cellular phenotype ( J:305430 )

♂N • immunofluorescent images of ATP5A (an outer mitochondria membrane marker) showed normal mitochondrial distribution in testicular sections at P25

abnormal male germ cell morphology ( J:305430 )

♂ • at P42, late-stage spermatocytes and round spermatids appear to gradually vacuolize

♂ • TEM analysis of adult testes showed mitochondrial swelling and fragmentation in male germ cells

teratozoospermia ( J:305430 )

♂ • only ~2% of epididymal sperm display normal morphology versus ~80% in wild-type controls

coiled sperm flagellum ( J:305430 )

♂ • ~14% of sperm exhibit a coiled tail

abnormal sperm head morphology ( J:305430 )

♂ • ~31% of sperm exhibit a bent head

absent sperm head ( J:305430 )

♂ • ~53% of sperm are acephalic

abnormal spermatid morphology ( J:305430 )

♂ • at P42, round spermatids are decreased in number and appear to gradually vacuolize

♂ • analysis of the mitochondrial aspect ratio (AR) distribution (where AR is ratio of the major axis to the minor axis of mitochondria) showed an increased % of short mitochondria in round spermatids

♂ • the distance between mitochondria and endoplasmic reticulum (ER) is increased by ~16% while the % of mitochondria-ER contacts is reduced by almost 50% and the ER-mitochondria contact coefficient (ERMICC) is reduced by >30% in round spermatids

abnormal spermatocyte morphology ( J:305430 )

♂ • at P42, late-stage spermatocytes are decreased in number and appear to gradually vacuolize

♂ • at P60, pachytene spermatocytes show a significantly increased thickness of the inter-mitochondrial cement (IMC)

♂ • at P18, immunostaining of calreticulin -- a mitochondria-associated ER membranes (MAMs) and ER marker protein -- showed a diffused granular pattern in the cytoplasm of spermatocytes instead of the continuous perinuclear localization seen in controls; at P60, calreticulin signals appear to be reduced and show diffused granular distribution

decreased male germ cell number ( J:305430 )

♂ • at P42, late-stage spermatocytes and round spermatids are decreased in number

oligozoospermia ( J:305430 )

♂ • adult males show a dramatic reduction in the number of spermatozoa retrieved from the cauda epididymis

abnormal endoplasmic reticulum morphology ( J:305430 )

♂ • at P60, round spermatids exhibit a fragmented ER structure instead of the tube-like cisternae structures seen in control spermatids

abnormal mitochondrial morphology ( J:305430 )

♂ • TEM analysis of adult testes showed mitochondrial swelling and fragmentation in male germ cells

♂ • at P60, pachytene spermatocytes show a significantly increased thickness of the inter-mitochondrial cement (IMC)

♂ • analysis of the mitochondrial aspect ratio (AR) distribution (where AR is ratio of the major axis to the minor axis of mitochondria) showed an increased % of short mitochondria in round spermatids

♂ • the distance between mitochondria and endoplasmic reticulum (ER) is increased by ~16% while mitochondria-ER contacts are reduced by almost 50% and the ER-mitochondria contact coefficient (ERMICC) is reduced by >30% in round spermatids

♂ • at P18, immunostaining of calreticulin -- a mitochondria-associated ER membranes (MAMs) and ER marker protein -- showed a diffused granular pattern in the cytoplasm of spermatocytes instead of the continuous perinuclear localization seen in controls; at P60, calreticulin signals appear to be reduced and show diffused granular distribution

increased mitochondrial DNA content ( J:305430 )

♂ • adult testes show a significant increase in mitochondrial DNA copy number at P60

increased testis apoptosis ( J:305430 )

♂ • TUNEL assays show a significantly increased number of apoptotic cells in the testes at P35 and P56

♂ • however, testis histology is normal at P7-P28 and no increase in apoptosis is noted at P14 and P28

abnormal mitochondrial ATP synthesis coupled electron transport ( J:305430 )

♂ • cytochrome c oxidase (COX, complex IV) activity is increased in adult testis sections

♂ • in contrast, succinate dehydrogenase (SDH, complex II) activity is normal

abnormal male germ cell physiology ( J:305430 )

♂ • male germ cells exhibit increased mitochondrial fission

increased male germ cell apoptosis ( J:305430 )

♂ • from P35, most male germ cells are gradually lost by apoptosis

increased mitochondrial fission ( J:305430 )

♂ • male germ cells exhibit increased mitochondrial fission

endocrine/exocrine glands

increased testis apoptosis ( J:305430 )

♂ • TUNEL assays show a significantly increased number of apoptotic cells in the testes at P35 and P56

♂ • however, testis histology is normal at P7-P28 and no increase in apoptosis is noted at P14 and P28

small seminiferous tubules ( J:305430 )

♂ • as adult males age, the number of severely atrophic seminiferous tubules is increased

seminiferous tubule degeneration ( J:305430 )

♂ • as adult males age, seminiferous tubules become severely atrophic and vacuolated (P60 to P120)

small testis ( J:305430 )

♂ • testes are significantly smaller at P56

decreased testis weight ( J:305430 )

♂ • testis weight/body weight ratio is significantly decreased from P35 to P120

Genotype
MGI:5763277

cn15

• Allelic Composition: Rhox^tm1Wilk/Rhox^tm1Wilk; Tg(RNU6-RNAi:Rhox3)2Wilk/0; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * FVB/NJ

reproductive system

decreased male germ cell number ( J:229199 )

♂ • dramatic reduction of post-meiotic germ cells

oligozoospermia ( J:229199 )

♂ • dramatic

abnormal seminiferous tubule morphology ( J:229199 )

♂

decreased testis weight ( J:229199 )

♂ • 80% reduction

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:229199 )

♂

decreased testis weight ( J:229199 )

♂ • 80% reduction

cellular

decreased male germ cell number ( J:229199 )

♂ • dramatic reduction of post-meiotic germ cells

oligozoospermia ( J:229199 )

♂ • dramatic

Genotype
MGI:5521299

cn16

• Allelic Composition: Piwil2^tm1.1Doca/Piwil2^tm2.1Doca; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * FVB/NJ

reproductive system

abnormal male germ cell apoptosis ( J:199259 )

♂ • especially in meiotic cells

decreased testis weight ( J:199259 )

♂

male infertility ( J:199259 )

♂

cellular

abnormal cell physiology ( J:199259 )

♂ • round spermatids fail to exhibit L1 transposon silencing unlike wild-type cells

abnormal male germ cell apoptosis ( J:199259 )

♂ • especially in meiotic cells

endocrine/exocrine glands

decreased testis weight ( J:199259 )

♂

Genotype
MGI:5521297

cn17

• Allelic Composition: Piwil2^tm2.1Doca/Piwil2^tm2.1Doca; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * FVB/NJ

reproductive system

abnormal male germ cell apoptosis ( J:199259 )

♂ • especially in meiotic cells

decreased testis weight ( J:199259 )

♂

male infertility ( J:199259 )

♂

cellular

abnormal cell physiology ( J:199259 )

♂ • round spermatids fail to exhibit L1 transposon silencing unlike wild-type cells

abnormal male germ cell apoptosis ( J:199259 )

♂ • especially in meiotic cells

endocrine/exocrine glands

decreased testis weight ( J:199259 )

♂

Genotype
MGI:5551619

cn18

• Allelic Composition: Kdm6b^tm1.1Iwam/Kdm6b^tm1.2Iwam; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB/NJ

Enlarged testes in Kdm6b^tm1.1Iwam/Kdm6b^tm1.2Iwam Tg(Stra8-icre)1Reb/0 males

cellular

abnormal spermatogonia morphology ( J:206350 )

♂ • increased Asingle spermatogonia in seminiferous tubules

♂ • frequent spermatogonial dedifferentiation

reproductive system

abnormal spermatogonia morphology ( J:206350 )

♂ • increased Asingle spermatogonia in seminiferous tubules

♂ • frequent spermatogonial dedifferentiation

enlarged testis ( J:206350 )

♂

delayed reproductive senescence ( J:206350 )

♂ • male mice sire pups much longer without a change in litter size compared with wild-type mice

♂ • however, litter production rate is normal

enhanced male fertility ( J:206350 )

♂ • male mice sire pups much longer without a change in litter size compared with wild-type mice

♂ • however, litter production rate is normal

endocrine/exocrine glands

enlarged testis ( J:206350 )

♂

Genotype
MGI:6888114

cn19

• Allelic Composition: Mgat1^tm2Jxm/Mgat1^tm2Jxm; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/NJ

reproductive system

azoospermia ( J:260130 )

♂ • at 28 dpp, no mature spermatozoa are present in testis sections

abnormal spermatid morphology ( J:260130 )

♂ • at 25 dpp, few elongated spermatids are observed

multinucleated giant male germ cells ( J:260130 )

♂ • at 24 and 25 dpp, fusion of cells adjacent to the lumen is observed in a few tubules

♂ • at 28 dpp, ~14% of tubules contain multinucleated cells composed of fused spermatids

arrest of spermatogenesis ( J:260130 )

♂ • starting at 24 and 25 dpp, fusion of cells adjacent to the lumen is observed in a few tubules

♂ • at 28 dpp, number of tubules with elongated spermatids is significantly decreased and multinucleated germ cells, but no mature spermatozoa, are present

♂ • premature upregulation of genes normally expressed later in spermatogenesis and spermiogenesis is observed at 22 and 23 dpp

♂ • EGFR and PDGFRA transcripts and ERK1/2 signaling are decreased in 22 dpp male germ cells

♂ • however, the number of Sertoli cells, spermatogonia, spermatocytes and stage VI and beyond tubules are relatively normal at 24-26 dpp

male infertility ( J:260130 )

♂

cellular

azoospermia ( J:260130 )

♂ • at 28 dpp, no mature spermatozoa are present in testis sections

abnormal spermatid morphology ( J:260130 )

♂ • at 25 dpp, few elongated spermatids are observed

multinucleated giant male germ cells ( J:260130 )

♂ • at 24 and 25 dpp, fusion of cells adjacent to the lumen is observed in a few tubules

♂ • at 28 dpp, ~14% of tubules contain multinucleated cells composed of fused spermatids

Genotype
MGI:6887929

cn20

• Allelic Composition: Agbl5^tm1.1Ics/Agbl5^tm1.1Ics; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6N

reproductive system

reproductive system phenotype ( J:271687 )

♂N • male mice are fertile, unlike male Agbl5^tm1.2Ics homozygotes

abnormal sperm axoneme morphology ( J:271687 )

♂ • splayed axonemes are observed

hairpin sperm flagellum ( J:271687 )

♂ • epididymal sperm show malformed sperm tails with hairpin bending (back-folded initial segments)

oligozoospermia ( J:271687 )

♂ • caudal epididymal sperm count is markedly reduced

detached acrosome ( J:271687 )

♂

abnormal sperm nucleus morphology ( J:271687 )

♂ • abnormally-shaped sperm nuclei and nuclear inclusions are observed

abnormal spermatid morphology ( J:271687 )

♂ • round and early elongating spermatids exhibit highly glutamylated microtubules

♂ • elongating spermatids have curly flagella and misshapen nuclei

♂ • number of elongating spermatids with supernumerary (>2) basal bodies is increased

abnormal manchette perinuclear ring morphology ( J:271687 )

♂ • absence of the perinuclear ring

abnormal seminiferous tubule morphology ( J:271687 )

♂ • spermatids are mislocalized at different stages throughout the different regions of the seminiferous tubules

♂ • a reduced number of mature spermatozoa are found in the lumen of the tubules

♂ • however, seminiferous tubule size is normal

abnormal spermiogenesis ( J:271687 )

♂ • testis tissue is disordered with spermatids of different developmental stages found mislocalized

♂ • various defects in spermiogenesis are observed at all stages from the early elongating spermatid stage to the condensed spermatid stage, similar to the ultrastructural phenotypes seen in male Agbl5^tm1.2Ics homozygotes

♂ • vacuolization of the cytoplasm and abnormal accumulation of cytoplasm in sperm cells with highly condensed nucleus is observed

♂ • however, assembly of sperm flagella is observed indicating partial maturation of sperm cells, unlike in male Agbl5^tm1.2Ics homozygotes

abnormal manchette assembly ( J:271687 )

♂ • disordered manchette microtubules and absence of the perinuclear ring and circumferential groove are observed

abnormal cauda epididymis morphology ( J:271687 )

♂ • a decreased number of mature spermatozoa and an increased number of precursor cells are found in the cauda epididymis

cellular

abnormal sperm axoneme morphology ( J:271687 )

♂ • splayed axonemes are observed

hairpin sperm flagellum ( J:271687 )

♂ • epididymal sperm show malformed sperm tails with hairpin bending (back-folded initial segments)

oligozoospermia ( J:271687 )

♂ • caudal epididymal sperm count is markedly reduced

detached acrosome ( J:271687 )

♂

abnormal sperm nucleus morphology ( J:271687 )

♂ • abnormally-shaped sperm nuclei and nuclear inclusions are observed

abnormal spermatid morphology ( J:271687 )

♂ • round and early elongating spermatids exhibit highly glutamylated microtubules

♂ • elongating spermatids have curly flagella and misshapen nuclei

♂ • number of elongating spermatids with supernumerary (>2) basal bodies is increased

abnormal manchette assembly ( J:271687 )

♂ • disordered manchette microtubules and absence of the perinuclear ring and circumferential groove are observed

abnormal manchette perinuclear ring morphology ( J:271687 )

♂ • absence of the perinuclear ring

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:271687 )

♂ • spermatids are mislocalized at different stages throughout the different regions of the seminiferous tubules

♂ • a reduced number of mature spermatozoa are found in the lumen of the tubules

♂ • however, seminiferous tubule size is normal

Genotype
MGI:6845052

cn21

• Allelic Composition: Csnk2b^tm1.1Bb/Csnk2b^tm1.2Bb; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S2/SvPasCrl * C57BL/6 * FVB/NJ

reproductive system

abnormal spermatid morphology ( J:289955 )

♂ • no round or elongated spermatids are detected in seminiferous tubules at 2 months of age

abnormal spermatocyte morphology ( J:289955 )

♂ • numbers of leptotene, zygotene and pachytene spermatocytes are significantly reduced in juvenile males

♂ • numbers of zygotene, pachytene and diplotene spermatocytes are significantly decreased at 2 months of age

♂ • however, numbers of spermatogonia and leptotene spermatocytes are normal at 2 months of age

decreased male germ cell number ( J:289955 )

♂ • number of germ cells per seminiferous tubule is significantly lower than that in controls at 12 dpp, 15 dpp and 17 dpp (corresponding to leptotene, zygotene and pachytene spermatocytes, respectively), and remains almost unchanged from 12 dpp to 17 dpp, unlike in control testes

♂ • number of MVH-positive germ cells is dramatically reduced at 2 months of age

azoospermia ( J:289955 )

♂ • no mature spermatozoa are present in the cauda epididymal lumens at 2 months of age

increased male germ cell apoptosis ( J:289955 )

♂ • number of TUNEL+ germ cells per seminiferous tubule is significantly increased at 2 months of age

increased testis apoptosis ( J:289955 )

♂ • more than 50% of the seminiferous tubules are TUNEL+ compared with less than 20% in control males

abnormal seminiferous tubule morphology ( J:289955 )

♂ • seminiferous tubules contain only a few spermatocytes at 12 dpp, 15 dpp and 17 dpp

♂ • only a few germ cells and no round or elongated spermatids are detected in seminiferous tubules at 2 months of age

small seminiferous tubules ( J:289955 )

♂ • seminiferous tubule diameter is reduced to half of that in control males at 2 months of age

small testis ( J:289955 )

♂ • testis size is markedly smaller at 2 months of age

decreased testis weight ( J:289955 )

♂ • testis weight-to-body weight ratio shows only small changes from day 12 to month 12 after birth and remains lower than that in controls at all ages examined

testicular atrophy ( J:289955 )

♂ • males develop testicular atrophy that does not change with increasing age after adulthood

arrest of spermatogenesis ( J:289955 )

♂ • first wave of spermatogenesis is severely blocked

male infertility ( J:289955 )

♂ • 8-week-old male mice fail to produce offspring during a 6-month mating period with wild-type females of known fertility

cellular

abnormal spermatid morphology ( J:289955 )

♂ • no round or elongated spermatids are detected in seminiferous tubules at 2 months of age

abnormal spermatocyte morphology ( J:289955 )

♂ • numbers of leptotene, zygotene and pachytene spermatocytes are significantly reduced in juvenile males

♂ • numbers of zygotene, pachytene and diplotene spermatocytes are significantly decreased at 2 months of age

♂ • however, numbers of spermatogonia and leptotene spermatocytes are normal at 2 months of age

decreased male germ cell number ( J:289955 )

♂ • number of germ cells per seminiferous tubule is significantly lower than that in controls at 12 dpp, 15 dpp and 17 dpp (corresponding to leptotene, zygotene and pachytene spermatocytes, respectively), and remains almost unchanged from 12 dpp to 17 dpp, unlike in control testes

♂ • number of MVH-positive germ cells is dramatically reduced at 2 months of age

azoospermia ( J:289955 )

♂ • no mature spermatozoa are present in the cauda epididymal lumens at 2 months of age

increased male germ cell apoptosis ( J:289955 )

♂ • number of TUNEL+ germ cells per seminiferous tubule is significantly increased at 2 months of age

increased testis apoptosis ( J:289955 )

♂ • more than 50% of the seminiferous tubules are TUNEL+ compared with less than 20% in control males

endocrine/exocrine glands

increased testis apoptosis ( J:289955 )

♂ • more than 50% of the seminiferous tubules are TUNEL+ compared with less than 20% in control males

abnormal seminiferous tubule morphology ( J:289955 )

♂ • seminiferous tubules contain only a few spermatocytes at 12 dpp, 15 dpp and 17 dpp

♂ • only a few germ cells and no round or elongated spermatids are detected in seminiferous tubules at 2 months of age

small seminiferous tubules ( J:289955 )

♂ • seminiferous tubule diameter is reduced to half of that in control males at 2 months of age

small testis ( J:289955 )

♂ • testis size is markedly smaller at 2 months of age

decreased testis weight ( J:289955 )

♂ • testis weight-to-body weight ratio shows only small changes from day 12 to month 12 after birth and remains lower than that in controls at all ages examined

testicular atrophy ( J:289955 )

♂ • males develop testicular atrophy that does not change with increasing age after adulthood

homeostasis/metabolism

abnormal protein level ( J:289955 )

♂ • Csnk2a2 mRNA expression and CSNK2A2 protein level is significantly decreased in testes

Genotype
MGI:6861833

cn22

• Allelic Composition: Ift27^{tm1c(EUCOMM)Hmgu}/Ift27^{tm1c(EUCOMM)Hmgu}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N * FVB/NJ
• Cell Lines: HEPD0653_7_E10

reproductive system

reproductive system phenotype ( J:251964 )

♂N • males exhibit no significant differences in testis weight or testis/body weight ratio relative to control males

decreased sperm progressive motility ( J:251964 )

♂ • only ~2% of epididymal sperm are motile but show a dramatic loss of progressive motility

asthenozoospermia ( J:251964 )

♂ • only ~2% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is severely reduced

immotile sperm ( J:251964 )

♂ • vast majority of epididymal sperm are immotile

abnormal testis physiology ( J:251964 )

♂ • testicular expression levels of IFT25 (the IFT27 binding partner) and IFT81 (a component of IFT-B complex) are significantly reduced

abnormal spermatogenesis ( J:251964 )

♂ • adult males show multiple signs of spermatogenesis failure during spermiogenesis

oligozoospermia ( J:251964 )

♂ • epididymal sperm count is severely reduced

teratozoospermia ( J:251964 )

♂ • sperm collected from the cauda epididymides show multiple abnormalities, including short, bent tails and round heads

♂ • however, sperm lipid raft distribution appears to be normal

abnormal sperm flagellum morphology ( J:251964 )

♂ • very few sperm appear to have a smooth tail; different light densities are observed along the whole tail

♂ • most sperm have vesicles/vacuoles in some area along the flagella

♂ • some epididymal sperm flagella have a distorted/damaged cell membrane

♂ • however, branched sperm flagella are never observed

abnormal outer dense fiber morphology ( J:251964 )

♂ • almost all epididymal sperm have misplaced or missing outer dense fibers (ODFs)

abnormal sperm axoneme morphology ( J:251964 )

♂ • TEM analysis showed that almost all epididymal sperm show a disrupted 9 + 2 core axoneme structure and a disorganized axoneme microtubule array

♂ • very few axoneme structures are detected in the seminiferous tubules

abnormal sperm end piece morphology ( J:251964 )

♂ • some sperm exhibit swollen tail tips

abnormal sperm flagellum thickness ( J:251964 )

♂ • uneven thickness of sperm tails in some areas

disorganized sperm mitochondrial sheath ( J:251964 )

♂ • TEM analysis of epididymal sperm showed that the mitochondria sheath is disorganized

abnormal sperm fibrous sheath morphology ( J:251964 )

♂ • TEM analysis of epididymal sperm showed that the fibrous sheath is disorganized

kinked sperm flagellum ( J:251964 )

♂ • bent sperm tails are observed

short sperm flagellum ( J:251964 )

♂

abnormal sperm head morphology ( J:251964 )

♂ • round and other misshapen sperm heads are observed

globozoospermia ( J:251964 )

♂ • round sperm heads are observed

abnormal spermiation ( J:251964 )

♂ • very few developed sperm are found in the lumen of seminiferous tubules

arrest of spermiogenesis ( J:251964 )

♂ • cauda epididymis lumen is filled with abnormal sperm heads, cytoplasm bodies, sloughed round spermatids, sloughed aggregates of elongating spermatids, numerous detached sperm heads and abnormal short sperm tails that appear disorganized

male infertility ( J:251964 )

♂ • when bred with adult wild-type females of known fertility, none of the 6-wk-old or adult males tested sired any pups/litters during a 2-month breeding period, indicating complete male sterility

cellular

oligozoospermia ( J:251964 )

♂ • epididymal sperm count is severely reduced

teratozoospermia ( J:251964 )

♂ • sperm collected from the cauda epididymides show multiple abnormalities, including short, bent tails and round heads

♂ • however, sperm lipid raft distribution appears to be normal

abnormal sperm flagellum morphology ( J:251964 )

♂ • very few sperm appear to have a smooth tail; different light densities are observed along the whole tail

♂ • most sperm have vesicles/vacuoles in some area along the flagella

♂ • some epididymal sperm flagella have a distorted/damaged cell membrane

♂ • however, branched sperm flagella are never observed

abnormal outer dense fiber morphology ( J:251964 )

♂ • almost all epididymal sperm have misplaced or missing outer dense fibers (ODFs)

abnormal sperm axoneme morphology ( J:251964 )

♂ • TEM analysis showed that almost all epididymal sperm show a disrupted 9 + 2 core axoneme structure and a disorganized axoneme microtubule array

♂ • very few axoneme structures are detected in the seminiferous tubules

abnormal sperm end piece morphology ( J:251964 )

♂ • some sperm exhibit swollen tail tips

abnormal sperm flagellum thickness ( J:251964 )

♂ • uneven thickness of sperm tails in some areas

disorganized sperm mitochondrial sheath ( J:251964 )

♂ • TEM analysis of epididymal sperm showed that the mitochondria sheath is disorganized

abnormal sperm fibrous sheath morphology ( J:251964 )

♂ • TEM analysis of epididymal sperm showed that the fibrous sheath is disorganized

kinked sperm flagellum ( J:251964 )

♂ • bent sperm tails are observed

short sperm flagellum ( J:251964 )

♂

abnormal sperm head morphology ( J:251964 )

♂ • round and other misshapen sperm heads are observed

globozoospermia ( J:251964 )

♂ • round sperm heads are observed

abnormal plasma membrane morphology ( J:251964 )

♂ • some epididymal sperm flagella have a distorted /damaged cell membrane

decreased sperm progressive motility ( J:251964 )

♂ • only ~2% of epididymal sperm are motile but show a dramatic loss of progressive motility

asthenozoospermia ( J:251964 )

♂ • only ~2% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is severely reduced

immotile sperm ( J:251964 )

♂ • vast majority of epididymal sperm are immotile

endocrine/exocrine glands

abnormal testis physiology ( J:251964 )

♂ • testicular expression levels of IFT25 (the IFT27 binding partner) and IFT81 (a component of IFT-B complex) are significantly reduced

Genotype
MGI:6865740

cn23

• Allelic Composition: Ift20^tm1.1Gjp/Ift20^tm1.2Gjp; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd * FVB/NJ

reproductive system

reproductive system phenotype ( J:265626 )

♂N • adult males exhibit no differences in testis-to-body weight ratio relative to control males

abnormal sperm motility ( J:265626 )

♂ • only a small % of sperm are motile and show forward motility, and flagellar movement is limited to a slow, erratic waveform with a very low amplitude

asthenozoospermia ( J:265626 )

♂ • only about 10% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is significantly reduced

immotile sperm ( J:265626 )

♂ • only about 10% of epididymal sperm are motile versus 80% in control males

abnormal seminiferous tubule morphology ( J:265626 )

♂ • very few flagellar axonemes or mature lysosomes are present in the seminiferous tubules; instead, cell debris, including degenerating chromatin and vacuoles are observed

abnormal spermatogenesis ( J:265626 )

♂ • very few germ cells complete spermatogenesis

♂ • however, testis histology revealed normal mitosis and meiosis

oligozoospermia ( J:265626 )

♂ • cauda epididymal sperm count is severely reduced

teratozoospermia ( J:265626 )

♂ • SEM analysis of epididymal sperm showed a variety of abnormal sperm morphologies, including short and kinked tails and round heads

abnormal sperm flagellum morphology ( J:265626 )

♂ • some epididymal sperm with kinked tails show excess retention of cytoplasm in the kinked area

abnormal outer dense fiber morphology ( J:265626 )

♂ • missing outer dense fibers (ODFs) are observed

abnormal sperm axoneme morphology ( J:265626 )

♂ • abnormal axonemal structures are frequently observed in epididymal sperm, including a disrupted 9 + 2 pattern and missing outer dense fibers (ODFs) in the axoneme

kinked sperm flagellum ( J:265626 )

♂ • many sperm tails are kinked

short sperm flagellum ( J:265626 )

♂ • many sperm tails are shortened

globozoospermia ( J:265626 )

♂ • some sperm display round, swollen heads

abnormal spermiogenesis ( J:265626 )

♂ • caudal epididymis shows a very low sperm concentration, with a high frequency of sperm anomalies, sloughed round germ cells, residual bodies, sperm with short tails, and sperm tails without heads

♂ • in testis, stage IX shows abnormal step 16 elongated spermatids that are not released into the lumen and residual bodies being sloughed into the lumen

♂ • stages I-III show abnormal elongated spermatids along with some normal heads and cytoplasm but spermatid tails do not appear in the lumen

♂ • stage X shows step 16 spermatid heads remaining in the seminiferous epithelium and residual bodies remaining at the lumen rather than being phagocytized

♂ • stage XI shows abnormal elongating spermatids and sloughed residual bodies remaining from prior stages

abnormal spermiation ( J:265626 )

♂ • stage X shows failure of spermiation with step 16 spermatid heads remaining in the seminiferous epithelium

decreased litter size ( J:265626 )

♂ • first litter size was significantly reduced in 37.5% of the 6-wk-old males that sired pups (2 to 5 pups/litter versus 7 to 11 pups/litter for age-matched control males)

male infertility ( J:265626 )

♂ • none of the 14 adult males tested produced any litters after 3 months of breeding with adult wild-type females of known fertility

♂ • however, sexual behavior is normal and vaginal plugs are observed in paired females

reduced male fertility ( J:265626 )

♂ • 6 of 16 (37.5%) of the 6-wk-old males tested were able to sire a single litter of significantly reduced size, but failed to sire pups again after the first litter

cellular

oligozoospermia ( J:265626 )

♂ • cauda epididymal sperm count is severely reduced

teratozoospermia ( J:265626 )

♂ • SEM analysis of epididymal sperm showed a variety of abnormal sperm morphologies, including short and kinked tails and round heads

abnormal sperm flagellum morphology ( J:265626 )

♂ • some epididymal sperm with kinked tails show excess retention of cytoplasm in the kinked area

abnormal outer dense fiber morphology ( J:265626 )

♂ • missing outer dense fibers (ODFs) are observed

abnormal sperm axoneme morphology ( J:265626 )

♂ • abnormal axonemal structures are frequently observed in epididymal sperm, including a disrupted 9 + 2 pattern and missing outer dense fibers (ODFs) in the axoneme

kinked sperm flagellum ( J:265626 )

♂ • many sperm tails are kinked

short sperm flagellum ( J:265626 )

♂ • many sperm tails are shortened

globozoospermia ( J:265626 )

♂ • some sperm display round, swollen heads

abnormal sperm motility ( J:265626 )

♂ • only a small % of sperm are motile and show forward motility, and flagellar movement is limited to a slow, erratic waveform with a very low amplitude

asthenozoospermia ( J:265626 )

♂ • only about 10% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is significantly reduced

immotile sperm ( J:265626 )

♂ • only about 10% of epididymal sperm are motile versus 80% in control males

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:265626 )

♂ • very few flagellar axonemes or mature lysosomes are present in the seminiferous tubules; instead, cell debris, including degenerating chromatin and vacuoles are observed

Genotype
MGI:6491901

cn24

• Allelic Composition: Mettl3^tm1.1Jhha/Mettl3^tm1.1Jhha; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S4/SvJaeSor * BALB/c * C57BL/6 * FVB/NJ

cellular

oligozoospermia ( J:299108 )

♂ • 75% reduction in sperm count in cauda epididymis

endocrine/exocrine glands

seminiferous tubule degeneration ( J:299108 )

♂ • mild degeneration

small testis ( J:299108 )

♂ • significant reduction in testis volume

reproductive system

oligozoospermia ( J:299108 )

♂ • 75% reduction in sperm count in cauda epididymis

seminiferous tubule degeneration ( J:299108 )

♂ • mild degeneration

small testis ( J:299108 )

♂ • significant reduction in testis volume

reduced male fertility ( J:299108 )

♂ • 75% reduction in sperm count in cauda epididymis

Genotype
MGI:6864146

cn25

• Allelic Composition: Ift74^{tm1c(EUCOMM)Hmgu}/Ift74^{tm1c(EUCOMM)Hmgu}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6N * FVB/NJ
• Cell Lines: HEPD0774_6_H07

reproductive system

reproductive system phenotype ( J:277145 )

♂N • adult males show no differences in testis-to-body weight ratio relative to control males

oligozoospermia ( J:277145 )

♂ • epididymal sperm count is dramatically reduced

teratozoospermia ( J:277145 )

♂ • all of the few sperm collected from the cauda epididymides show a variety of abnormalities, including very short tails and mostly abnormally shaped heads

abnormal sperm axoneme morphology ( J:277145 )

♂ • spermatids show a variety of axonemal abnormalities in the seminiferous tubules, including a complete absence of the core axoneme, disorganized microtubules, clusters of microtubules, and abnormally formed axonemes without the central microtubules

absent sperm axonemal central pair ( J:277145 )

♂ • abnormally formed axonemes without the central microtubules are observed

absent sperm flagellum ( J:277145 )

♂ • step 11 and 13 elongating spermatids lack tails

short sperm flagellum ( J:277145 )

♂ • all epididymal sperm have very short tails

abnormal sperm head morphology ( J:277145 )

♂ • most epididymal sperm have grossly abnormal heads

♂ • elongating spermatids show round and distorted heads

♂ • however, acrosome formation appears to be normal

abnormal spermatid morphology ( J:277145 )

♂ • elongating spermatids show round and distorted heads and absence of tails

asthenozoospermia ( J:277145 )

♂ • only ~2% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is significantly reduced

immotile sperm ( J:277145 )

♂ • vast majority of epididymal sperm are immotile

abnormal seminiferous tubule morphology ( J:277145 )

♂ • seminiferous tubule lumen is almost empty, unlike in control tubules where sperm are found in the lumen

abnormal testis physiology ( J:277145 )

♂ • testicular expression of IFT81 protein (a major IFT74 binding partner) and components of other IFT complex proteins (IFT27, IFT57, IFT88, and IFT140) are significantly reduced

♂ • AKAP4 (a processed form of the major component of the fibrous sheath) is also significantly reduced

abnormal spermiogenesis ( J:277145 )

♂ • stage XI seminiferous tubules show abnormal step 11 spermatids with abnormally shaped heads and absence of tails

♂ • step 13 elongating spermatids lack tails while excess cytoplasm appears to be sloughed into the lumen

♂ • cauda epididymal lumen is filled with massive amounts of large abnormal cytoplasmic bodies, residual bodies, sloughed round cells, and abnormal spermatids with short or absent tails

abnormal spermiation ( J:277145 )

♂ • failure of spermiation in stage VIII, with abnormal step 16 spermatids being phagocytized, although step 8 round spermatids and pachytene spermatocytes look normal in the same tubule

♂ • residual bodies are not formed but small pieces of germ cell cytoplasm are retained at the luminal border

male infertility ( J:277145 )

♂ • when bred with adult wild-type females of known fertility for at least 2 months, none of the adult males tested sired any pups/litters, indicating complete male sterility

cellular

oligozoospermia ( J:277145 )

♂ • epididymal sperm count is dramatically reduced

teratozoospermia ( J:277145 )

♂ • all of the few sperm collected from the cauda epididymides show a variety of abnormalities, including very short tails and mostly abnormally shaped heads

abnormal sperm axoneme morphology ( J:277145 )

♂ • spermatids show a variety of axonemal abnormalities in the seminiferous tubules, including a complete absence of the core axoneme, disorganized microtubules, clusters of microtubules, and abnormally formed axonemes without the central microtubules

absent sperm axonemal central pair ( J:277145 )

♂ • abnormally formed axonemes without the central microtubules are observed

absent sperm flagellum ( J:277145 )

♂ • step 11 and 13 elongating spermatids lack tails

short sperm flagellum ( J:277145 )

♂ • all epididymal sperm have very short tails

abnormal sperm head morphology ( J:277145 )

♂ • most epididymal sperm have grossly abnormal heads

♂ • elongating spermatids show round and distorted heads

♂ • however, acrosome formation appears to be normal

abnormal spermatid morphology ( J:277145 )

♂ • elongating spermatids show round and distorted heads and absence of tails

asthenozoospermia ( J:277145 )

♂ • only ~2% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is significantly reduced

immotile sperm ( J:277145 )

♂ • vast majority of epididymal sperm are immotile

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:277145 )

♂ • seminiferous tubule lumen is almost empty, unlike in control tubules where sperm are found in the lumen

abnormal testis physiology ( J:277145 )

♂ • testicular expression of IFT81 protein (a major IFT74 binding partner) and components of other IFT complex proteins (IFT27, IFT57, IFT88, and IFT140) are significantly reduced

♂ • AKAP4 (a processed form of the major component of the fibrous sheath) is also significantly reduced

Genotype
MGI:6755500

cn26

• Allelic Composition: Fis1^tm1Dcc/Fis1^tm1.1Dcc; Gt(ROSA)26Sor^{tm1.1(CAG-COX8A/Dendra2)Dcc}/Gt(ROSA)26Sor⁺; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/NJ

reproductive system

azoospermia ( J:309044 )

♂ • no spermatozoa in epididymides

abnormal spermatid morphology ( J:309044 )

♂ • impaired acrosome development and failure to produce elongated spermatids

multinucleated giant male germ cells ( J:309044 )

♂ • with increased mitochondria content

increased male germ cell apoptosis ( J:309044 )

♂ • 4-fold increase in tubules

small testis ( J:309044 )

♂

decreased testis weight ( J:309044 )

♂

cellular

azoospermia ( J:309044 )

♂ • no spermatozoa in epididymides

abnormal spermatid morphology ( J:309044 )

♂ • impaired acrosome development and failure to produce elongated spermatids

multinucleated giant male germ cells ( J:309044 )

♂ • with increased mitochondria content

increased mitochondrial number ( J:309044 )

♂ • in round spermatids and giant cells

impaired autophagy ( J:309044 )

♂ • in round spermatids and giant cells with aberrant accumulation of autophagic structures

increased male germ cell apoptosis ( J:309044 )

♂ • 4-fold increase in tubules

homeostasis/metabolism

impaired autophagy ( J:309044 )

♂ • in round spermatids and giant cells with aberrant accumulation of autophagic structures

endocrine/exocrine glands

small testis ( J:309044 )

♂

decreased testis weight ( J:309044 )

♂

Genotype
MGI:7286183

cn27

• Allelic Composition: Huwe1^tm1Alas/Y; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/NJ

reproductive system

abnormal spermatocyte morphology ( J:323709 )

♂ • at 48 days post retinoic acid injection (48dpRA), synchronized adult testes contain fewer Stra8+ pre-leptotene spermatocytes (located away from the basement membrane of the tubules), indicating a defect in spermatogonial differentiation

♂ • at 8 days post retinoic acid injection (8dpRA), synchronized testes show clear loss of pre-leptotene/leptotene spermatocytes (germ cells located away from the basement membrane) in the tubules

♂ • at 8dpRA, the average number of Stra8+ pre-leptotene spermatocytes is significantly reduced in synchronized testes, whereas the number of Stra8+ spermatogonia (located adjacent to the basement membrane) is normal

♂ • staining with SYCP3 (a marker used to identify different types of spermatocytes in meiotic prophase I) confirmed the presence of fewer leptotene spermatocytes at 8dpRA

♂ • at 10 days post-partum (dpp), unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci

abnormal spermatogonia morphology ( J:323709 )

♂ • at 48dpRA, spermatogonia differentiation is disrupted in synchronized adult testes, leading to formation of fewer pre-leptotene spermatocytes

♂ • at 48dpRA, expression of markers for differentiating spermatogonia (Stra8, Dazl, Sohlh2) is markedly reduced in synchronized adult testes

♂ • at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci

decreased male germ cell number ( J:323709 )

♂ • significant loss of differentiating spermatogonia, spermatocytes and extensive loss of spermatids are observed in the tubules at 4 months of age

oligozoospermia ( J:323709 )

♂ • average cauda epididymal sperm number is only 3% of that in control males

abnormal male meiosis ( J:323709 )

♂ • at 8dpRA, the proportion of proliferating Stra8+ pre-leptotene spermatocytes is reduced by ~50% while expression of early meiotic markers (Spo11, Smc1b, Sycp1, Sycp3) is significantly decreased in synchronized testes, indicating impaired entry into meiosis

increased testis apoptosis ( J:323709 )

♂ • at 8dpRA, synchronized testes show a significantly higher % of TUNEL+ tubules than control testes; similar results are obtained by staining the same sections with cleaved, activated caspase 3

abnormal male germ cell physiology ( J:323709 )

♂ • at 8dpRA, the proportion of proliferating Stra8+ pre-leptotene spermatocytes incorporating BrdU in synchronized testes is ~50% lower than in control testes

♂ • however, no difference is noted in the proportion of proliferating Stra8+ A1 spermatogonia at 8dpRA

increased male germ cell apoptosis ( J:323709 )

♂ • at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci, along with recruitment of pCHK2 to these gammaH2AX foci, indicating activation of the DNA damage response pathway

♂ • at 8dpRA, double staining for Tra98 (a germ cell marker) and cleaved caspase 3 showed a significant increase in male germ cell apoptosis in synchronized testes relative to control testes (~68% versus 46%, respectively)

♂ • no significant colocalization of p53 with gammaH2AX foci is observed, suggesting p53-independent apoptosis

small testis ( J:323709 )

♂ • adult males have significantly smaller testes than control males

decreased testis weight ( J:323709 )

♂ • average weight of adult testes is only 30% of control males

arrest of spermatogenesis ( J:323709 )

♂ • at 4 months of age, males show significant loss of differentiating spermatogonia, spermatocytes and extensive loss of spermatids in the seminiferous tubules, indicating a developmental arrest early in spermatogenesis

abnormal caput epididymis morphology ( J:323709 )

♂ • few sperm are present in the caput epididymis

male infertility ( J:323709 )

♂ • males fail to sire any litters during a 4-week fertility assay

♂ • however, the frequency of vaginal plugging is normal

cellular

abnormal spermatocyte morphology ( J:323709 )

♂ • at 48 days post retinoic acid injection (48dpRA), synchronized adult testes contain fewer Stra8+ pre-leptotene spermatocytes (located away from the basement membrane of the tubules), indicating a defect in spermatogonial differentiation

♂ • at 8 days post retinoic acid injection (8dpRA), synchronized testes show clear loss of pre-leptotene/leptotene spermatocytes (germ cells located away from the basement membrane) in the tubules

♂ • at 8dpRA, the average number of Stra8+ pre-leptotene spermatocytes is significantly reduced in synchronized testes, whereas the number of Stra8+ spermatogonia (located adjacent to the basement membrane) is normal

♂ • staining with SYCP3 (a marker used to identify different types of spermatocytes in meiotic prophase I) confirmed the presence of fewer leptotene spermatocytes at 8dpRA

♂ • at 10 days post-partum (dpp), unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci

abnormal spermatogonia morphology ( J:323709 )

♂ • at 48dpRA, spermatogonia differentiation is disrupted in synchronized adult testes, leading to formation of fewer pre-leptotene spermatocytes

♂ • at 48dpRA, expression of markers for differentiating spermatogonia (Stra8, Dazl, Sohlh2) is markedly reduced in synchronized adult testes

♂ • at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci

decreased male germ cell number ( J:323709 )

♂ • significant loss of differentiating spermatogonia, spermatocytes and extensive loss of spermatids are observed in the tubules at 4 months of age

oligozoospermia ( J:323709 )

♂ • average cauda epididymal sperm number is only 3% of that in control males

abnormal male meiosis ( J:323709 )

♂ • at 8dpRA, the proportion of proliferating Stra8+ pre-leptotene spermatocytes is reduced by ~50% while expression of early meiotic markers (Spo11, Smc1b, Sycp1, Sycp3) is significantly decreased in synchronized testes, indicating impaired entry into meiosis

increased testis apoptosis ( J:323709 )

♂ • at 8dpRA, synchronized testes show a significantly higher % of TUNEL+ tubules than control testes; similar results are obtained by staining the same sections with cleaved, activated caspase 3

abnormal male germ cell physiology ( J:323709 )

♂ • at 8dpRA, the proportion of proliferating Stra8+ pre-leptotene spermatocytes incorporating BrdU in synchronized testes is ~50% lower than in control testes

♂ • however, no difference is noted in the proportion of proliferating Stra8+ A1 spermatogonia at 8dpRA

increased male germ cell apoptosis ( J:323709 )

♂ • at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci, along with recruitment of pCHK2 to these gammaH2AX foci, indicating activation of the DNA damage response pathway

♂ • at 8dpRA, double staining for Tra98 (a germ cell marker) and cleaved caspase 3 showed a significant increase in male germ cell apoptosis in synchronized testes relative to control testes (~68% versus 46%, respectively)

♂ • no significant colocalization of p53 with gammaH2AX foci is observed, suggesting p53-independent apoptosis

endocrine/exocrine glands

increased testis apoptosis ( J:323709 )

♂ • at 8dpRA, synchronized testes show a significantly higher % of TUNEL+ tubules than control testes; similar results are obtained by staining the same sections with cleaved, activated caspase 3

small testis ( J:323709 )

♂ • adult males have significantly smaller testes than control males

decreased testis weight ( J:323709 )

♂ • average weight of adult testes is only 30% of control males

Genotype
MGI:5473319

cn28

• Allelic Composition: Rxfp2^tm1Aia/Rxfp2^{tm1c(EUCOMM)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6N * FVB/NJ

reproductive system

reproductive system phenotype ( J:194006 )

N • mice exhibit normal reproductive organ abnormalities

Genotype
MGI:6510020

cn29

• Allelic Composition: Spata19^tm1Lij/Spata19^tm1Lij; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB/NJ

reproductive system

abnormal sperm flagellum morphology ( J:301706 )

♂ • all sperm show tail defects

abnormal sperm mitochondrial sheath morphology ( J:301706 )

♂ • severe defects in the sheaths in the midpiece

abnormal sperm mitochondrial morphology ( J:301706 )

♂ • mitochondria are variable in size and have an irregular appearance

decreased sperm progressive motility ( J:301706 )

♂ • severely reduced

male infertility ( J:301706 )

♂ • males are infertile despite displaying normal mating behavior

♂ • male infertility can be bypassed using intracytoplasmic sperm injection

cellular

abnormal sperm flagellum morphology ( J:301706 )

♂ • all sperm show tail defects

abnormal sperm mitochondrial sheath morphology ( J:301706 )

♂ • severe defects in the sheaths in the midpiece

abnormal sperm mitochondrial morphology ( J:301706 )

♂ • mitochondria are variable in size and have an irregular appearance

decreased sperm progressive motility ( J:301706 )

♂ • severely reduced

abnormal respiratory electron transport chain ( J:301706 )

♂ • significant decrease in the relative activities of the mitochondrial respiratory chain complex IV and lower ATP levels in sperm samples

Genotype
MGI:5559510

cn30

• Allelic Composition: Ppp1cc^tm1Lex/Ppp1cc^tm1Lex; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S/SvEvBrd * FVB/NJ

reproductive system

reproductive system phenotype ( J:203985 )

♀N • female mice exhibit normal fertility

oligozoospermia ( J:203985 )

♂ • a few tubules contain spermatozoa in their lumen

teratozoospermia ( J:203985 )

♂

abnormal sperm mitochondrial sheath morphology ( J:203985 )

♂

kinked sperm flagellum ( J:203985 )

♂ • between the midpiece and principal pieces

asthenozoospermia ( J:203985 )

♂

male infertility ( J:203985 )

♂

cellular

oligozoospermia ( J:203985 )

♂ • a few tubules contain spermatozoa in their lumen

teratozoospermia ( J:203985 )

♂

abnormal sperm mitochondrial sheath morphology ( J:203985 )

♂

kinked sperm flagellum ( J:203985 )

♂ • between the midpiece and principal pieces

asthenozoospermia ( J:203985 )

♂

Genotype
MGI:7281440

cn31

• Allelic Composition: Ppp4c^em1Qys/Ppp4c^em1Qys; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * FVB/NJ

reproductive system

abnormal sperm midpiece morphology ( J:309155 )

♂ • tail bending (head-bent-back) is consistently observed in the midpiece of the sperm tail

♂ • cytoplasmic remnants are attached to the midpiece

♂ • however, mitochondrial sheath assembly is normal

kinked sperm flagellum ( J:309155 )

♂ • ~91% of spermatozoa in the testes and cauda epididymis exhibit abnormal tail bending (head-bent-back)

♂ • bending sites are always observed in the midpiece of the tail, not in the head or principal piece

♂ • TEM analysis showed that the tail bent at the midpiece is held together by tissues resembling remnants of cytoplasm

oligozoospermia ( J:309155 )

♂ • at 2 months of age, the total number of sperm in the cauda epididymes is decreased by ~50% relative to that in controls males

abnormal spermatocyte morphology ( J:309155 )

♂ • TUNEL staining showed significant spermatocyte cell loss in the seminiferous epithelium

♂ • however, spermatogonia cell survival is normal

increased male germ cell apoptosis ( J:309155 )

♂ • TUNEL staining showed a significant increase in the number of apoptotic cells in the testes relative to control males

♂ • TUNEL+ signals are colocalized with the spermatocyte cell marker synaptonemal complex protein-3 (SYCP3), but not with the spermatogonia cell marker ZBTB16 (aka PLZF), indicating spermatocyte cell loss in the seminiferous epithelium

decreased sperm progressive motility ( J:309155 )

♂ • at 2 months of age, the percentage of progressive sperm is markedly reduced

asthenozoospermia ( J:309155 )

♂ • at 2 months of age, the percentage of motile sperm is markedly reduced

abnormal seminiferous tubule morphology ( J:309155 )

♂ • some seminiferous tubules appear disorganized with large vacuoles while others show normal tubule structure in histology

small testis ( J:309155 )

♂ • at 2 months of age, testes size is significantly smaller than in control males

decreased testis weight ( J:309155 )

♂ • weight of adult testes is significantly lower than in control males

♂ • however, adult body weight is normal

arrest of spermiogenesis ( J:309155 )

♂ • cytoplasmic remnants are abnormally retained on the bent midpiece, indicating a defect in cytoplasm removal from elongated spermatids which in turn leads to the failure of spermiogenesis

♂ • however, many aspects of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheath arrangement and 9 + 2 flagellar structure assembly, are normal

male infertility ( J:309155 )

♂ • when mated with wild-type females, adult male mice do not produce any progeny despite normal vaginal plug formation

♂ • male infertility can be overcome by intracytoplasmic injection-embryo transfer (ICSI-ET) but male offspring is sub-fertile

impaired fertilization ( J:309155 )

♂ • although tail-bending spermatozoa are found in the vaginal plug after natural mating, no sperm are found in COCs of oviductal ampullae and no two pronuclei formation is observed

♂ • in an IVF assay, the number of spermatozoa bound to the zona pellucida is significantly decreased and sperm fail to fertilize the eggs and develop to the 2-cell stage

decreased fertilization frequency ( J:309155 )

♂ • spermatozoa fail to fertilize eggs by natural mating or IVF

impaired binding of sperm to zona pellucida ( J:309155 )

♂ • the number of spermatozoa bound to the zona pellucida of metaphase II oocytes is significantly decreased after IVF

cellular

abnormal sperm midpiece morphology ( J:309155 )

♂ • tail bending (head-bent-back) is consistently observed in the midpiece of the sperm tail

♂ • cytoplasmic remnants are attached to the midpiece

♂ • however, mitochondrial sheath assembly is normal

kinked sperm flagellum ( J:309155 )

♂ • ~91% of spermatozoa in the testes and cauda epididymis exhibit abnormal tail bending (head-bent-back)

♂ • bending sites are always observed in the midpiece of the tail, not in the head or principal piece

♂ • TEM analysis showed that the tail bent at the midpiece is held together by tissues resembling remnants of cytoplasm

oligozoospermia ( J:309155 )

♂ • at 2 months of age, the total number of sperm in the cauda epididymes is decreased by ~50% relative to that in controls males

abnormal spermatocyte morphology ( J:309155 )

♂ • TUNEL staining showed significant spermatocyte cell loss in the seminiferous epithelium

♂ • however, spermatogonia cell survival is normal

increased male germ cell apoptosis ( J:309155 )

♂ • TUNEL staining showed a significant increase in the number of apoptotic cells in the testes relative to control males

♂ • TUNEL+ signals are colocalized with the spermatocyte cell marker synaptonemal complex protein-3 (SYCP3), but not with the spermatogonia cell marker ZBTB16 (aka PLZF), indicating spermatocyte cell loss in the seminiferous epithelium

decreased sperm progressive motility ( J:309155 )

♂ • at 2 months of age, the percentage of progressive sperm is markedly reduced

asthenozoospermia ( J:309155 )

♂ • at 2 months of age, the percentage of motile sperm is markedly reduced

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:309155 )

♂ • some seminiferous tubules appear disorganized with large vacuoles while others show normal tubule structure in histology

small testis ( J:309155 )

♂ • at 2 months of age, testes size is significantly smaller than in control males

decreased testis weight ( J:309155 )

♂ • weight of adult testes is significantly lower than in control males

♂ • however, adult body weight is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oligoasthenoteratozoospermia		DOID:0070311		J:309155

Genotype
MGI:6883592

cn32

• Allelic Composition: Atg5^tm1Myok/Atg5^tm1Myok; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129S/SvEv * FVB/NJ

reproductive system

oligozoospermia ( J:307712 )

♂ • cauda epididymal sperm number is reduced by ~60% relative to controls

teratozoospermia ( J:307712 )

♂ • cauda epididymal sperm show multiple abnormalities, including distorted and round heads, abnormal flagella, double heads, and sperm bundles

abnormal sperm flagellum morphology ( J:307712 )

♂ • 20-30% of cauda epididymal sperm display abnormal flagella

abnormal sperm end piece morphology ( J:307712 )

♂ • some epididymal sperm show a short flagellum with a bulb at the tip of the tail

abnormal sperm midpiece morphology ( J:307712 )

♂ • some cauda epididymal sperm exhibit a discontinuous accessory structure in the midpiece

♂ • some sperm show a large vesicle at the midpiece

♂ • cross-sections of two or more axonemes are seen in one cell, some of which are surrounded with disconnected mitochondria

abnormal sperm mitochondrial sheath morphology ( J:307712 )

♂ • mitochondria staining of cauda epididymal sperm revealed abnormal mitochondrial sheath formation: discontinuous and bundle forms of mitochondria signals are observed

absent sperm fibrous sheath ( J:307712 )

♂ • 23.12% sperm exhibit unsheathed flagella at the principal piece

short sperm flagellum ( J:307712 )

♂ • some epididymal sperm show a short flagellum with a bulb at the tip of the tail

abnormal sperm head morphology ( J:307712 )

♂ • ~50% of cauda epididymal sperm display misshapen heads, including round, swollen or bent heads

♂ • in some sperm, significant mitochondrial staining is present at the head region, suggesting that the middle pieces and tails are coiling around the heads

abnormal acrosome assembly ( J:307712 )

♂ • cauda epididymal sperm exhibit abnormal acrosome formation: peanut-lectin (an acrosome marker) aggregates around the nucleus indicating abnormal acrosome localization

♂ • TEM analysis revealed abnormally shaped acrosomes in developing spermatids

globozoospermia ( J:307712 )

♂ • distorted and round heads are observed

abnormal sperm nucleus morphology ( J:307712 )

♂ • cauda epididymal sperm exhibit an abnormally formed chromatin structure

double-headed sperm ( J:307712 )

♂ • some sperm exhibit double heads

multinucleated giant male germ cells ( J:307712 )

♂ • some elongating spermatids fuse into giant cells

asthenozoospermia ( J:307712 )

♂ • only few sperm are motile but exhibit markedly reduced motility

immotile sperm ( J:307712 )

♂ • only a small % of epididymal sperm are motile versus >80% in controls

decreased testis weight ( J:307712 )

♂ • adult testis-to-body weight ratio is slightly lower than that of control males

abnormal testis physiology ( J:307712 )

♂ • testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity

abnormal spermiogenesis ( J:307712 )

♂ • spermatogenesis defects are first observed in step 10-14 elongating spermatids

♂ • abnormal nuclear shapes start appearing with mixing of step 9 and 12 spermatids in stage XII

♂ • large residual bodies are sloughed into the lumen and found even in stages XI-XI

♂ • step 16 spermatids show retention in the epithelium in stages IX-XII

♂ • some elongating spermatids fuse into giant cells; multiple elongating spermatids are wrapped in one cell membrane, indicating failure of individualization

♂ • sloughing of cytoplasm or cytoplasm with attached immature elongating spermatids into the lumen is observed

♂ • however, no major defects are observed in mitosis or meiosis

abnormal sperm individualization ( J:307712 )

♂ • 33.29% of epididymal sperm aggregate into sperm bundles

♂ • cauda epididymal sperm show loss of sperm individualization: two or more axonemes are frequently wrapped in one cell membrane

♂ • in the seminiferous tubules, multiple elongating spermatids share a single cell membrane indicating failure of individualization

abnormal spermiation ( J:307712 )

♂ • step 16 spermatids show retention in the epithelium rather than being released by spermiation in stages IX-XII

♂ • impaired release of sperm into the seminiferous tubule lumen is likely due to failure to remove intercellular bridge components, as a result of disrupted autophagy activity

abnormal cauda epididymis morphology ( J:307712 )

♂ • cauda epididymal lumen is filled with sloughed germ cells, large cytoplasmic bodies, and spermatozoa with disorganized heads and tails

male infertility ( J:307712 )

♂ • 3 of six 2-mo-old males did not sire any offspring during 1 month of mating with wild-type females

♂ • 9 of 11 older males did not sire any pups through 3 months of breeding

reduced male fertility ( J:307712 )

♂ • 3 of six 2-mo-old males sired only 5, 1, and 8 pups, respectively, totaling 14 pups during one month of mating with wild-type females

♂ • one 3- to 5-month-old male sired 10 pups and one 5- to 7-month-old male sired one pup, respectively, through 3 months of breeding

cellular

oligozoospermia ( J:307712 )

♂ • cauda epididymal sperm number is reduced by ~60% relative to controls

teratozoospermia ( J:307712 )

♂ • cauda epididymal sperm show multiple abnormalities, including distorted and round heads, abnormal flagella, double heads, and sperm bundles

abnormal sperm flagellum morphology ( J:307712 )

♂ • 20-30% of cauda epididymal sperm display abnormal flagella

abnormal sperm end piece morphology ( J:307712 )

♂ • some epididymal sperm show a short flagellum with a bulb at the tip of the tail

abnormal sperm midpiece morphology ( J:307712 )

♂ • some cauda epididymal sperm exhibit a discontinuous accessory structure in the midpiece

♂ • some sperm show a large vesicle at the midpiece

♂ • cross-sections of two or more axonemes are seen in one cell, some of which are surrounded with disconnected mitochondria

abnormal sperm mitochondrial sheath morphology ( J:307712 )

♂ • mitochondria staining of cauda epididymal sperm revealed abnormal mitochondrial sheath formation: discontinuous and bundle forms of mitochondria signals are observed

absent sperm fibrous sheath ( J:307712 )

♂ • 23.12% sperm exhibit unsheathed flagella at the principal piece

short sperm flagellum ( J:307712 )

♂ • some epididymal sperm show a short flagellum with a bulb at the tip of the tail

abnormal sperm head morphology ( J:307712 )

♂ • ~50% of cauda epididymal sperm display misshapen heads, including round, swollen or bent heads

♂ • in some sperm, significant mitochondrial staining is present at the head region, suggesting that the middle pieces and tails are coiling around the heads

abnormal acrosome assembly ( J:307712 )

♂ • cauda epididymal sperm exhibit abnormal acrosome formation: peanut-lectin (an acrosome marker) aggregates around the nucleus indicating abnormal acrosome localization

♂ • TEM analysis revealed abnormally shaped acrosomes in developing spermatids

globozoospermia ( J:307712 )

♂ • distorted and round heads are observed

abnormal sperm nucleus morphology ( J:307712 )

♂ • cauda epididymal sperm exhibit an abnormally formed chromatin structure

double-headed sperm ( J:307712 )

♂ • some sperm exhibit double heads

multinucleated giant male germ cells ( J:307712 )

♂ • some elongating spermatids fuse into giant cells

impaired autophagy ( J:307712 )

♂ • testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity

asthenozoospermia ( J:307712 )

♂ • only few sperm are motile but exhibit markedly reduced motility

immotile sperm ( J:307712 )

♂ • only a small % of epididymal sperm are motile versus >80% in controls

homeostasis/metabolism

impaired autophagy ( J:307712 )

♂ • testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity

endocrine/exocrine glands

decreased testis weight ( J:307712 )

♂ • adult testis-to-body weight ratio is slightly lower than that of control males

abnormal testis physiology ( J:307712 )

♂ • testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity

Genotype
MGI:5475537

cn33

• Allelic Composition: Rdh10^{tm1c(KOMP)Wtsi}/Rdh10^{tm1c(KOMP)Wtsi}; Tg(Amh-cre)8815Reb/0; Tg(RARE-Hspa1b/lacZ)12Jrt/0; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * CD-1 * FVB/N * SJL

reproductive system

small testis ( J:193281 )

♂

abnormal male reproductive system physiology ( J:193281 )

♂ • lack of retinoic acid

endocrine/exocrine glands

small testis ( J:193281 )

♂

Genotype
MGI:6864067

cn34

• Allelic Composition: Ift81^{tm1c(EUCOMM)Wtsi}/Ift81^{tm1c(EUCOMM)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * FVB/NJ
• Cell Lines: EPD0382_4_F06

reproductive system

reproductive system phenotype ( J:292151 )

♂N • adult males exhibit no differences in testis-to-body weight ratio relative to control males

abnormal sperm flagellum morphology ( J:292151 )

♂

abnormal sperm axoneme morphology ( J:292151 )

♂ • sperm tail forms without an axonemal complex of microtubules in the core

abnormal sperm midpiece morphology ( J:292151 )

♂ • tail of elongating spermatids displays abnormal alignment of the outer dense fibers and mitochondria around the absent axoneme

disorganized sperm mitochondrial sheath ( J:292151 )

♂ • sperm mitochondrial sheath appears disorganized

abnormal sperm fibrous sheath morphology ( J:292151 )

♂ • abnormal aggregates of fibrous sheath components are sometimes seen in areas bulging away from the core

kinked sperm flagellum ( J:292151 )

♂ • some sperm tails appear to be kinked

short sperm flagellum ( J:292151 )

♂ • all of the few epididymal sperm present exhibit short tails

oligozoospermia ( J:292151 )

♂ • cauda epididymal sperm density is markedly reduced

abnormal sperm head morphology ( J:292151 )

♂ • elongating spermatids exhibit abnormal head morphology

abnormal acrosome morphology ( J:292151 )

♂ • in areas of nucleopod formation, the acrosome shows abnormal folding at the indented region of the nucleus

♂ • however, acrosome biogenesis is normal

abnormal sperm nucleus morphology ( J:292151 )

♂ • in elongating spermatids with abnormal heads, nuclei are condensed but exhibit abnormal shapes, with extensions of nucleopods that are surrounded by the acrosome

multinucleated giant male germ cells ( J:292151 )

♂ • numerous multinucleated giant germ cells are found in the lumen of seminiferous tubules and epididymis

asthenozoospermia ( J:292151 )

♂ • only ~2% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is significantly reduced

immotile sperm ( J:292151 )

♂ • vast majority of epididymal sperm are immotile

abnormal seminiferous tubule epithelium morphology ( J:292151 )

♂ • ultrastructural changes are observed in the seminiferous epithelium, including elongating spermatids with abnormal heads

abnormal testis physiology ( J:292151 )

♂ • testicular expression levels of most IFT components (IFT20, IFT25, IFT27, IFT57, IFT74 and IFT88) are significantly decreased; AKAP4 (a processed form of the major component of the fibrous sheath) is also reduced

abnormal spermiogenesis ( J:292151 )

♂ • cauda epididymis lumen is filled with large cytoplasmic bodies, sloughed spermatids, and rare sperm with abnormal heads and short or absent tails

♂ • only limited acetylated tubulin staining is detected, indicating few sperm tails in the epididymal lumen; most clusters in the lumen are DAPI-negative, indicating residual bodies

♂ • numerous multinucleated giant germ cells are seen in the lumen of seminiferous tubules and epididymis

♂ • however, TUNEL staining showed no increase in apoptotic cells in seminiferous tubules

abnormal spermiation ( J:292151 )

♂ • evidence of failure of spermiation is observed with the heads of thin, highly condensed step 16 spermatids pulled deep into the seminiferous epithelium

male infertility ( J:292151 )

♂ • after 2 months of breeding with adult wild-type females of known fertility, none of the adult males tested sired any pups, indicating complete male sterility

♂ • however, sexual behavior is normal and vaginal plugs are observed in the paired females

cellular

abnormal sperm flagellum morphology ( J:292151 )

♂

abnormal sperm axoneme morphology ( J:292151 )

♂ • sperm tail forms without an axonemal complex of microtubules in the core

abnormal sperm midpiece morphology ( J:292151 )

♂ • tail of elongating spermatids displays abnormal alignment of the outer dense fibers and mitochondria around the absent axoneme

disorganized sperm mitochondrial sheath ( J:292151 )

♂ • sperm mitochondrial sheath appears disorganized

abnormal sperm fibrous sheath morphology ( J:292151 )

♂ • abnormal aggregates of fibrous sheath components are sometimes seen in areas bulging away from the core

kinked sperm flagellum ( J:292151 )

♂ • some sperm tails appear to be kinked

short sperm flagellum ( J:292151 )

♂ • all of the few epididymal sperm present exhibit short tails

oligozoospermia ( J:292151 )

♂ • cauda epididymal sperm density is markedly reduced

abnormal sperm head morphology ( J:292151 )

♂ • elongating spermatids exhibit abnormal head morphology

abnormal acrosome morphology ( J:292151 )

♂ • in areas of nucleopod formation, the acrosome shows abnormal folding at the indented region of the nucleus

♂ • however, acrosome biogenesis is normal

abnormal sperm nucleus morphology ( J:292151 )

♂ • in elongating spermatids with abnormal heads, nuclei are condensed but exhibit abnormal shapes, with extensions of nucleopods that are surrounded by the acrosome

multinucleated giant male germ cells ( J:292151 )

♂ • numerous multinucleated giant germ cells are found in the lumen of seminiferous tubules and epididymis

asthenozoospermia ( J:292151 )

♂ • only ~2% of epididymal sperm are motile but their motility, calculated as curvilinear velocity (VCL), is significantly reduced

immotile sperm ( J:292151 )

♂ • vast majority of epididymal sperm are immotile

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:292151 )

♂ • ultrastructural changes are observed in the seminiferous epithelium, including elongating spermatids with abnormal heads

abnormal testis physiology ( J:292151 )

♂ • testicular expression levels of most IFT components (IFT20, IFT25, IFT27, IFT57, IFT74 and IFT88) are significantly decreased; AKAP4 (a processed form of the major component of the fibrous sheath) is also reduced

Genotype
MGI:5475535

cn35

• Allelic Composition: Rdh10^{tm1c(KOMP)Wtsi}/Rdh10^{tm1c(KOMP)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * FVB/NJ * SJL

reproductive system

reproductive system phenotype ( J:193281 )

♂N • testes weight and morphology are indistinguishable from controls at 2 and 3 weeks of age

Genotype
MGI:5475536

cn36

• Allelic Composition: Rdh10^{tm1c(KOMP)Wtsi}/Rdh10^{tm1c(KOMP)Wtsi}; Tg(Amh-cre)8815Reb/0; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * FVB/N * SJL

reproductive system

abnormal spermatogonia morphology ( J:193281 )

♂ • block of differentiation of Aal spermatogonia into A1 spermatogonia at 2 and 3 weeks of age

abnormal seminiferous tubule morphology ( J:193281 )

♂ • most tubules are devoid of meiotic cells at 2 and 3 weeks of age, retaining only undifferentiated spermatogonia-like cells and Sertoli cells

♂ • however, by 9 weeks of age, tubules contain the expected spermatogonia, spermatocytes, and spermatids

seminiferous tubule degeneration ( J:193281 )

♂ • over 85% of tubules are degenerated at 2 and 3 weeks of age

small testis ( J:193281 )

♂ • at 2 and 3 weeks of age

decreased testis weight ( J:193281 )

♂ • dramatically lower at 2 and 3 weeks of age compared to wild-type controls and homozygous mice carrying only one of the cre transgenes

abnormal spermatogenesis ( J:193281 )

♂ • most tubules are devoid of meiotic cells at 2 and 3 weeks of age, retaining only undifferentiated spermatogonia-like cells and Sertoli cells

♂ • treatment with retinoic acid enhances synchrony of spermatogenesis

♂ • however, by 9 weeks of age, spermatogenesis is similar to controls

♂ • in adults only 1 of 48 males shows spermatogenesis with an altered stage frequency

arrest of male meiosis ( J:193281 )

♂ • fail to initiate meiosis at 2 and 3 weeks of age

abnormal male reproductive system physiology ( J:193281 )

♂ • numerous degenerated germ cells are present in the testes at 2 and 3 weeks of age

reduced male fertility ( J:193281 )

♂ • males under 7 weeks of age are infertile or subfertile

♂ • however, mice over 9 weeks of age are fertile and produce litters similar in size to controls

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:193281 )

♂ • most tubules are devoid of meiotic cells at 2 and 3 weeks of age, retaining only undifferentiated spermatogonia-like cells and Sertoli cells

♂ • however, by 9 weeks of age, tubules contain the expected spermatogonia, spermatocytes, and spermatids

seminiferous tubule degeneration ( J:193281 )

♂ • over 85% of tubules are degenerated at 2 and 3 weeks of age

small testis ( J:193281 )

♂ • at 2 and 3 weeks of age

decreased testis weight ( J:193281 )

♂ • dramatically lower at 2 and 3 weeks of age compared to wild-type controls and homozygous mice carrying only one of the cre transgenes

cellular

abnormal spermatogonia morphology ( J:193281 )

♂ • block of differentiation of Aal spermatogonia into A1 spermatogonia at 2 and 3 weeks of age

arrest of male meiosis ( J:193281 )

♂ • fail to initiate meiosis at 2 and 3 weeks of age

Genotype
MGI:6864268

cn37

• Allelic Composition: Racgap1^tm1Mahi/Racgap1^tm1Mahi; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * FVB/NJ

reproductive system

abnormal spermatogonia morphology ( J:206583 )

♂ • massive reduction in PLZF-positive undifferentiated spermatogonia pool, starting from 6 dpp

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

decreased male germ cell number ( J:206583 )

♂ • severe decrease in differentiated spermatogonia and primary spermatocytes, with massive reduction in PLZF-positive undifferentiated spermatogonia at 12 dpp

♂ • depletion of germ cell lineage with presence of multinucleated germ cells in pre-pubertal testes at 6, 8, 10 and 12 dpp

azoospermia ( J:206583 )

♂ • no spermatozoa are present in the epididymis or testes

multinucleated giant male germ cells ( J:206583 )

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

♂ • TEM confirmed presence of several syncytial spermatogonia at 10 dpp

♂ • however, all nuclei are properly individualized, indicating normal karyokinesis

abnormal spermatogonia proliferation ( J:206583 )

♂ • marked reduction in Ki67-positive cells at 12 dpp, indicating a division defect of spermatogonial cells that results in multi-nucleated cells and further proliferation arrest

abnormal seminiferous tubule morphology ( J:206583 )

♂ • at 45 dpp, ~91.5% of seminiferous tubules are abnormal with numerous large vacuoles and either (i) lack a germ cell layer, (ii) exhibit a single type of spermatocytes or spermatids, or (iii) contain only Sertoli cells and spermatogonia

abnormal Sertoli cell morphology ( J:206583 )

♂ • at 45 dpp, all testes show large Sertoli cell vacuolization

seminiferous tubule degeneration ( J:206583 )

♂ • at 45 dpp, many seminiferous tubules are markedly atrophic with a decreased number of spermatocytes, spermatids and spermatozoa

small testis ( J:206583 )

♂ • drastic reduction in testis size, starting from 10 to 12 dpp

decreased testis weight ( J:206583 )

♂ • at 45 dpp, mean testes weight is 21.1 mg relative to 68.3 mg in control males

abnormal testis physiology ( J:206583 )

♂ • number of TUNEL-positive cells is significantly reduced in pre-pubertal testes at 10 and 12 dpp

arrest of spermatogenesis ( J:206583 )

♂ • failure to form permanent intercellular bridges in the germ cell lineage induces a spermatogenesis arrest in the PLZF-positive population of undifferentiated spermatogonia

male infertility ( J:206583 )

♂ • all males are sterile

♂ • however, sexual behavior is normal and vaginal plugs are observed in mated females

cellular

abnormal spermatogonia morphology ( J:206583 )

♂ • massive reduction in PLZF-positive undifferentiated spermatogonia pool, starting from 6 dpp

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

decreased male germ cell number ( J:206583 )

♂ • severe decrease in differentiated spermatogonia and primary spermatocytes, with massive reduction in PLZF-positive undifferentiated spermatogonia at 12 dpp

♂ • depletion of germ cell lineage with presence of multinucleated germ cells in pre-pubertal testes at 6, 8, 10 and 12 dpp

azoospermia ( J:206583 )

♂ • no spermatozoa are present in the epididymis or testes

multinucleated giant male germ cells ( J:206583 )

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

♂ • TEM confirmed presence of several syncytial spermatogonia at 10 dpp

♂ • however, all nuclei are properly individualized, indicating normal karyokinesis

abnormal spermatogonia proliferation ( J:206583 )

♂ • marked reduction in Ki67-positive cells at 12 dpp, indicating a division defect of spermatogonial cells that results in multi-nucleated cells and further proliferation arrest

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:206583 )

♂ • at 45 dpp, ~91.5% of seminiferous tubules are abnormal with numerous large vacuoles and either (i) lack a germ cell layer, (ii) exhibit a single type of spermatocytes or spermatids, or (iii) contain only Sertoli cells and spermatogonia

abnormal Sertoli cell morphology ( J:206583 )

♂ • at 45 dpp, all testes show large Sertoli cell vacuolization

seminiferous tubule degeneration ( J:206583 )

♂ • at 45 dpp, many seminiferous tubules are markedly atrophic with a decreased number of spermatocytes, spermatids and spermatozoa

small testis ( J:206583 )

♂ • drastic reduction in testis size, starting from 10 to 12 dpp

decreased testis weight ( J:206583 )

♂ • at 45 dpp, mean testes weight is 21.1 mg relative to 68.3 mg in control males

abnormal testis physiology ( J:206583 )

♂ • number of TUNEL-positive cells is significantly reduced in pre-pubertal testes at 10 and 12 dpp

Genotype
MGI:7287839

cn38

• Allelic Composition: Hnrnpk^tm1.1Cya/Hnrnpk^tm1.1Cya; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * FVB/NJ

reproductive system

arrest of male meiosis ( J:324169 )

♂ • spermatocytes undergo progressive depletion during meiotic prophase

increased male germ cell apoptosis ( J:324169 )

♂

small testis ( J:324169 )

♂ • starting at P14

decreased testis weight ( J:324169 )

♂

small caput epididymis ( J:324169 )

♂

small cauda epididymis ( J:324169 )

♂

male infertility ( J:324169 )

♂

growth/size/body

decreased body size ( J:324169 )

♂ • starting at P14 in male mice

endocrine/exocrine glands

small testis ( J:324169 )

♂ • starting at P14

decreased testis weight ( J:324169 )

♂

cellular

arrest of male meiosis ( J:324169 )

♂ • spermatocytes undergo progressive depletion during meiotic prophase

increased male germ cell apoptosis ( J:324169 )

♂

Genotype
MGI:7266812

cn39

• Allelic Composition: Tardbp^tm1.1Pcw/Tardbp^tm1.1Pcw; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * FVB/NJ * SJL

reproductive system

teratozoospermia ( J:324061 )

♂ • most cauda epididymal sperm are morphologically abnormal

abnormal sperm flagellum morphology ( J:324061 )

♂ • ~55% of sperm tails are curved/bent

abnormal sperm head morphology ( J:324061 )

♂ • roughly 50% of cauda sperm show deformed or detached heads

♂ • ~55% of sperm show head and midpiece bent over the principal piece of the tail

absent sperm head ( J:324061 )

♂ • headless sperm are observed

decreased male germ cell number ( J:324061 )

♂ • extensive male germ cell depletion is observed at P35

♂ • germ cell depletion is progressively worse at 3, 7, and 21 months of age

oligozoospermia ( J:324061 )

♂ • males exhibit 7.4 times less cauda epididymal sperm than control males

abnormal chromosomal synapsis ( J:324061 )

♂ • diplotene-like spermatocytes display nonhomologous chromosome synapsis

♂ • zygotene-like spermatocytes show nonhomologous chromosome synapsis, short chromosome length, and abnormal number of chromosomes

♂ • pachytene-like spermatocytes show nonhomologous chromosome synapsis, with persistent gammaH2AX flares/foci on autosomes likely indicating unrepaired double-strand DNA breaks

increased male germ cell apoptosis ( J:324061 )

♂ • TUNEL staining showed a significant increase in spermatocyte apoptosis

abnormal seminiferous tubule epithelium morphology ( J:324061 )

♂ • vacuole formation is observed within the seminiferous epithelium at P35

♂ • at advanced ages, the seminiferous epithelium only consists of Sertoli cells

♂ • onset of seminiferous epithelium pathology with reduced cellularity is at P12

small seminiferous tubules ( J:324061 )

♂ • at P35, the seminiferous tubule diameter appears narrower than in control males

♂ • a 1.6-fold reduction in tubule cross-section diameter is seen at 3 months of age

seminiferous tubule degeneration ( J:324061 )

♂ • atrophy of the seminiferous tubules, germ cell loss, and vacuole formation are observed at P35

♂ • vacuole formation is progressively worse at 3, 7, and 21 months of age

small testis ( J:324061 )

♂ • testis size is severely decreased at P35

decreased testis weight ( J:324061 )

♂ • a 2.9-fold reduction in testis weight is seen at 3 months of age

arrest of spermatogenesis ( J:324061 )

♂ • at P35, spermatogonia and a few meiotic cells can be seen but no round spermatids are detected

♂ • at 3-4 months of age, flow cytometry data showed a significant decrease in 1N cells (round spermatids) and an increase in 2N (spermatogonia, Sertoli, peritubular, and Leydig cells) and 4N (primary spermatocytes) cells, indicating arrest in meiosis

arrest of male meiosis ( J:324061 )

♂ • spermatocytes show failure to complete prophase I of meiosis with arrest at the mid-pachytene stage

reduced male fertility ( J:324061 )

♂ • 3-month-old males are severely subfertile, producing a significantly lower number of litters than control males over a 6-month period (0.6 litters versus 6 litters, respectively)

cellular

teratozoospermia ( J:324061 )

♂ • most cauda epididymal sperm are morphologically abnormal

abnormal sperm flagellum morphology ( J:324061 )

♂ • ~55% of sperm tails are curved/bent

abnormal sperm head morphology ( J:324061 )

♂ • roughly 50% of cauda sperm show deformed or detached heads

♂ • ~55% of sperm show head and midpiece bent over the principal piece of the tail

absent sperm head ( J:324061 )

♂ • headless sperm are observed

decreased male germ cell number ( J:324061 )

♂ • germ cell depletion is progressively worse at 3, 7, and 21 months of age

♂ • extensive male germ cell depletion is observed at P35

oligozoospermia ( J:324061 )

♂ • males exhibit 7.4 times less cauda epididymal sperm than control males

abnormal chromosome morphology ( J:324061 )

♂ • zygotene-like spermatocytes show short chromosome length and abnormal number of chromosomes

♂ • some pachytene-like spermatocytes show abnormally long chromosomes

abnormal chromosome number ( J:324061 )

♂ • zygotene-like spermatocytes show abnormal number of chromosomes likely due to abnormal synapsis between nonhomologous chromosomes

abnormal chromosomal synapsis ( J:324061 )

♂ • diplotene-like spermatocytes display nonhomologous chromosome synapsis

♂ • zygotene-like spermatocytes show nonhomologous chromosome synapsis, short chromosome length, and abnormal number of chromosomes

♂ • pachytene-like spermatocytes show nonhomologous chromosome synapsis, with persistent gammaH2AX flares/foci on autosomes likely indicating unrepaired double-strand DNA breaks

arrest of male meiosis ( J:324061 )

♂ • spermatocytes show failure to complete prophase I of meiosis with arrest at the mid-pachytene stage

increased male germ cell apoptosis ( J:324061 )

♂ • TUNEL staining showed a significant increase in spermatocyte apoptosis

abnormal double-strand DNA break repair ( J:324061 )

♂ • pachytene-like spermatocytes with synapsis defects show gammaH2AX foci/flares on autosomes, indicating delayed DSB repair

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:324061 )

♂ • vacuole formation is observed within the seminiferous epithelium at P35

♂ • at advanced ages, the seminiferous epithelium only consists of Sertoli cells

♂ • onset of seminiferous epithelium pathology with reduced cellularity is at P12

small seminiferous tubules ( J:324061 )

♂ • at P35, the seminiferous tubule diameter appears narrower than in control males

♂ • a 1.6-fold reduction in tubule cross-section diameter is seen at 3 months of age

seminiferous tubule degeneration ( J:324061 )

♂ • atrophy of the seminiferous tubules, germ cell loss, and vacuole formation are observed at P35

♂ • vacuole formation is progressively worse at 3, 7, and 21 months of age

small testis ( J:324061 )

♂ • testis size is severely decreased at P35

decreased testis weight ( J:324061 )

♂ • a 2.9-fold reduction in testis weight is seen at 3 months of age

homeostasis/metabolism

abnormal double-strand DNA break repair ( J:324061 )

♂ • pachytene-like spermatocytes with synapsis defects show gammaH2AX foci/flares on autosomes, indicating delayed DSB repair

Genotype
MGI:6830505

cn40

• Allelic Composition: Ewsr1^{tm1c(EUCOMM)Wtsi}/Ewsr1^{tm1d(EUCOMM)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6J

cellular

azoospermia ( J:314468 )

♂

abnormal meiosis ( J:314468 )

♂ • In spermatocytes the number of double stranded breaks, indicated by DMC1 foci, is normal in early leptotene and zygotene but double stranded repair is delayed, PRDM-dependent hotspots differ somewhat from controls, and there are increased unsynapsed chromosomes

arrest of male meiosis ( J:314468 )

♂ • meiosis is blocked at pachynema/diplonema, with normal proportions of leptotene and zygotene spermatocytes, no spermatocytes are found in seminiferous tubules beyond prophase 1, and there is increased apoptotic germ cells in testes

abnormal DNA methylation during gametogenesis ( J:314468 )

♂ • spermatocytes show decreased PRDM9-dependent H3K4 and H3K36 trimethylation: decreased H3K4me3 in leptonema and zygonema and slightly decreased H3K36me3 in leptonema and zygonema but not diplonema; H3K4me3 ChIP-seq from spermatocytes identified fewer than normal peaks, with approximately 38.7% of hotspot peaks missing, in particular those with low H3K4 trimethylation in controls; reduced levels of H3K36 trimethylation, particularly in intergenic region hotspots

reproductive system

azoospermia ( J:314468 )

♂

abnormal meiosis ( J:314468 )

♂ • In spermatocytes the number of double stranded breaks, indicated by DMC1 foci, is normal in early leptotene and zygotene but double stranded repair is delayed, PRDM-dependent hotspots differ somewhat from controls, and there are increased unsynapsed chromosomes

abnormal DNA methylation during gametogenesis ( J:314468 )

♂ • spermatocytes show decreased PRDM9-dependent H3K4 and H3K36 trimethylation: decreased H3K4me3 in leptonema and zygonema and slightly decreased H3K36me3 in leptonema and zygonema but not diplonema; H3K4me3 ChIP-seq from spermatocytes identified fewer than normal peaks, with approximately 38.7% of hotspot peaks missing, in particular those with low H3K4 trimethylation in controls; reduced levels of H3K36 trimethylation, particularly in intergenic region hotspots

small testis ( J:314468 )

♂

decreased testis weight ( J:314468 )

♂ • decreased testes weight in adults but not at 14 or 18 days of age

arrest of spermatogenesis ( J:314468 )

♂

arrest of male meiosis ( J:314468 )

♂ • meiosis is blocked at pachynema/diplonema, with normal proportions of leptotene and zygotene spermatocytes, no spermatocytes are found in seminiferous tubules beyond prophase 1, and there is increased apoptotic germ cells in testes

male infertility ( J:314468 )

♂

endocrine/exocrine glands

small testis ( J:314468 )

♂

decreased testis weight ( J:314468 )

♂ • decreased testes weight in adults but not at 14 or 18 days of age

Genotype
MGI:6457270

cn41

• Allelic Composition: Pramex1^{tm1c(KOMP)Wtsi}/Y; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6J * C57BL/6N

reproductive system

reproductive system phenotype ( J:290700 )

♂N • mature males are fertile with a normal pregnancy rate and litter size; sperm motility is normal at both 4 and 12 months of age

decreased male germ cell number ( J:290700 )

♂ • a decrease in the number of germ cells is first noted in a few seminiferous tubules at P14 and becomes obvious at P21

♂ • by P35, Sertoli cellonly (SCO) tubules are observed in some of the affected tubules

♂ • at P21, TRA98+ germ cells and SOX9+ Sertoli cells are present, whereas DDX4+ germ cells are completely or partially lost, suggesting that the lost germ cells in affected tubules are primarily spermatocytes

increased male germ cell apoptosis ( J:290700 )

♂ • number of TUNEL+ germ cells is significantly increased at P7, reaches a peak level at P14 and then drops at P21; by P35, number of TUNEL+ germ cells is reduced to basal levels seen in control mice

♂ • at P14, TUNEL/DDX4 dual-staining suggests that apoptotic cells found in the lumen of seminiferous tubules are predominantly pachytene spermatocytes

increased testis apoptosis ( J:290700 )

♂ • % of apoptotic TUNEL+ seminiferous tubules is significantly increased at P7 and P14, but not at P21 and P35

abnormal seminiferous tubule morphology ( J:290700 )

♂ • at P35, Sertoli cell-only (SCO) tubules and abnormal lumen are observed; affected tubules are frequently located at the periphery of testes

♂ • % of abnormal seminiferous tubules is significantly increased at P35 and P120 relative to controls, with 5-7% of tubules being affected

♂ • at P120 and P365, most of the affected tubules exhibit an abnormal lumen

ectopic Sertoli cells ( J:290700 )

♂ • at P120, the frequency of misplaced Sertoli cells away from the basal side of the tubule is significantly increased relative to controls

♂ • however, the number of Sertoli cells is unaffected at P21, P35, and P120

small testis ( J:290700 )

♂ • males show a significant (12%) reduction in tests size at P120

decreased testis weight ( J:290700 )

♂ • testis weight and testis index (testis weight/body weight x 100) begin to diverge at P21; a gradual reduction in testis weight is observed from P21 to P56 when maximum testis weight is reached

♂ • at P120, testis weight and testis index are, respectively, 12.35% and 8.20% lower than in control mice

abnormal spermatogenesis ( J:290700 )

♂ • males show germ cell loss in the affected seminiferous tubules during the first and subsequent rounds of spermatogenesis

oligozoospermia ( J:290700 )

♂ • epididymal sperm count is significantly reduced by 13% at 4 months, but not at 12 months of age

abnormal spermatocyte morphology ( J:290700 )

♂ • at P21, TRA98+ germ cells and SOX9+ Sertoli cells are present, whereas DDX4+ germ cells are completely or partially lost, suggesting that the lost germ cells in abnormal tubules are primarily spermatocytes

arrest of spermatogenesis ( J:290700 )

♂ • germ cell arrest at spermatogonia stage for other affected tubules in mature mice

endocrine/exocrine glands

increased testis apoptosis ( J:290700 )

♂ • % of apoptotic TUNEL+ seminiferous tubules is significantly increased at P7 and P14, but not at P21 and P35

abnormal seminiferous tubule morphology ( J:290700 )

♂ • at P35, Sertoli cell-only (SCO) tubules and abnormal lumen are observed; affected tubules are frequently located at the periphery of testes

♂ • % of abnormal seminiferous tubules is significantly increased at P35 and P120 relative to controls, with 5-7% of tubules being affected

♂ • at P120 and P365, most of the affected tubules exhibit an abnormal lumen

ectopic Sertoli cells ( J:290700 )

♂ • at P120, the frequency of misplaced Sertoli cells away from the basal side of the tubule is significantly increased relative to controls

♂ • however, the number of Sertoli cells is unaffected at P21, P35, and P120

small testis ( J:290700 )

♂ • males show a significant (12%) reduction in tests size at P120

decreased testis weight ( J:290700 )

♂ • testis weight and testis index (testis weight/body weight x 100) begin to diverge at P21; a gradual reduction in testis weight is observed from P21 to P56 when maximum testis weight is reached

♂ • at P120, testis weight and testis index are, respectively, 12.35% and 8.20% lower than in control mice

cellular

abnormal spermatocyte morphology ( J:290700 )

♂ • at P21, TRA98+ germ cells and SOX9+ Sertoli cells are present, whereas DDX4+ germ cells are completely or partially lost, suggesting that the lost germ cells in abnormal tubules are primarily spermatocytes

decreased male germ cell number ( J:290700 )

♂ • a decrease in the number of germ cells is first noted in a few seminiferous tubules at P14 and becomes obvious at P21

♂ • by P35, Sertoli cellonly (SCO) tubules are observed in some of the affected tubules

♂ • at P21, TRA98+ germ cells and SOX9+ Sertoli cells are present, whereas DDX4+ germ cells are completely or partially lost, suggesting that the lost germ cells in affected tubules are primarily spermatocytes

oligozoospermia ( J:290700 )

♂ • epididymal sperm count is significantly reduced by 13% at 4 months, but not at 12 months of age

increased male germ cell apoptosis ( J:290700 )

♂ • number of TUNEL+ germ cells is significantly increased at P7, reaches a peak level at P14 and then drops at P21; by P35, number of TUNEL+ germ cells is reduced to basal levels seen in control mice

♂ • at P14, TUNEL/DDX4 dual-staining suggests that apoptotic cells found in the lumen of seminiferous tubules are predominantly pachytene spermatocytes

increased testis apoptosis ( J:290700 )

♂ • % of apoptotic TUNEL+ seminiferous tubules is significantly increased at P7 and P14, but not at P21 and P35

Genotype
MGI:6887371

cn42

• Allelic Composition: Slc9a8^{tm1c(KOMP)Wtsi}/Slc9a8^{tm1c(KOMP)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/NJ
• Cell Lines: EPD0033_5_A07

reproductive system

reproductive system phenotype ( J:245977 )

♂N • males show no significant changes in the morphology and diameter of seminiferous tubules relative to control males

♂N • ~5% of spermatozoa are NHE8-positive and show intact acrosomes and elongated nuclei in some tubules; this is attributed to the known ~95% deletion efficiency of Stra8-iCre mice

abnormal sperm mitochondrial sheath morphology ( J:245977 )

♂ • spermatozoa show abnormal mitochondrial distribution, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

absent sperm mitochondrial sheath ( J:245977 )

♂ • MitoTracker staining revealed loss of the mitochondrial sheath, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

abnormal sperm head morphology ( J:245977 )

♂ • in mature spermatozoa, DNA is condensed but sperm heads are not elongated and lack acrosomal caps

abnormal acrosome assembly ( J:245977 )

♂ • acrosome biogenesis is impaired, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

abnormal proacrosomal vesicle fusion ( J:245977 )

♂ • although electron-dense vesicles accumulate between the Golgi and the nuclear envelope, no acrosomal granules or acrosomal caps are found, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

globozoospermia ( J:245977 )

♂ • round-headed spermatozoa are observed, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

absent acrosome ( J:245977 )

♂ • round-headed sperm lack acrosomes, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

male infertility ( J:245977 )

♂ • males are infertile, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

cellular

abnormal sperm mitochondrial sheath morphology ( J:245977 )

♂ • spermatozoa show abnormal mitochondrial distribution, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

absent sperm mitochondrial sheath ( J:245977 )

♂ • MitoTracker staining revealed loss of the mitochondrial sheath, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

abnormal sperm head morphology ( J:245977 )

♂ • in mature spermatozoa, DNA is condensed but sperm heads are not elongated and lack acrosomal caps

abnormal acrosome assembly ( J:245977 )

♂ • acrosome biogenesis is impaired, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

abnormal proacrosomal vesicle fusion ( J:245977 )

♂ • although electron-dense vesicles accumulate between the Golgi and the nuclear envelope, no acrosomal granules or acrosomal caps are found, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

globozoospermia ( J:245977 )

♂ • round-headed spermatozoa are observed, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

absent acrosome ( J:245977 )

♂ • round-headed sperm lack acrosomes, similar to Slc9a8^{tm1d(KOMP)Wtsi} homozygotes

Genotype
MGI:7327651

cn43

• Allelic Composition: Mfn2^em1Cya/Mfn2^em1Cya; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6J * FVB/NJ

reproductive system

abnormal sperm mitochondrial sheath morphology ( J:324164 )

♂ • spermatocytes exhibit aggregation of mitochondria with disrupted respiratory chain compared with control cells

kinked sperm flagellum ( J:324164 )

♂ • folded or broken tails

abnormal sperm nucleus morphology ( J:324164 )

♂

abnormal male meiosis ( J:324164 )

♂ • abnormal progression from the zygotene to pachytene stages and impaired crossing over

small seminiferous tubules ( J:324164 )

♂ • reduced diameter

small testis ( J:324164 )

♂

endocrine/exocrine glands

small seminiferous tubules ( J:324164 )

♂ • reduced diameter

small testis ( J:324164 )

♂

cellular

abnormal sperm mitochondrial sheath morphology ( J:324164 )

♂ • spermatocytes exhibit aggregation of mitochondria with disrupted respiratory chain compared with control cells

kinked sperm flagellum ( J:324164 )

♂ • folded or broken tails

abnormal sperm nucleus morphology ( J:324164 )

♂

abnormal male meiosis ( J:324164 )

♂ • abnormal progression from the zygotene to pachytene stages and impaired crossing over

Genotype
MGI:5702983

cn44

• Allelic Composition: Ranbp9^tm1Wyan/Ranbp9^tm1Wyan; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6J * FVB/NJ

reproductive system

abnormal sperm flagellum morphology ( J:222184 )

♂ • epididymal sperm shows a variety of morphological abnormalities in the flagellum including coiled or headless flagellum

coiled sperm flagellum ( J:222184 )

♂

abnormal sperm head morphology ( J:222184 )

♂ • epididymal sperm shows a variety of morphological abnormalities in the sperm head like crooked, round, or bent heads

decreased male germ cell number ( J:222184 )

♂ • seminiferous epithelium is thinner in 3 month old testes and contains numerous vacuoles, indicative of germ cell depletion

♂ • presence of numerous degenerating/degenerated spermatids, or even spermatocytes in the epididymis; this enhanced depletion of spermatocytes and spermatids and the production of deformed spermatozoa are seen only in mice older than 2 months and no differences are seen during the first wave of spermatogenesis

♂ • proportional increase of meiotic cells (i.e.spermatocytes) and decrease in haploid cells (spermatids) despite lowered total cell number in both populations, indicating active depletion of spermatocytes and spermatids

oligozoospermia ( J:222184 )

♂ • sperm counts are lower in 12 week old males

increased male germ cell apoptosis ( J:222184 )

♂ • about 2-fold increase in apoptotic cells, mainly spermatocytes and early round spermatids, in the testes

♂ • seminiferous tubules at around stage VI exhibit round spermatids with an increase in unrepaired DNA double-strand breaks

decreased sperm progressive motility ( J:222184 )

♂

asthenozoospermia ( J:222184 )

♂ • total motility and progressive motility of sperm are reduced in 12 week old males

abnormal seminiferous tubule epithelium morphology ( J:222184 )

♂ • seminiferous epithelium is thinner in 3 month old testes and contains numerous vacuoles

small testis ( J:222184 )

♂ • 12 week old males exhibit reduced testis size

decreased testis weight ( J:222184 )

♂ • 12 week old males exhibit reduced testis weight

small caput epididymis ( J:222184 )

♂

small epididymis ( J:222184 )

♂ • caput and cauda epididymides are smaller

reduced male fertility ( J:222184 )

♂ • males exhibit reduced fertility in 5-month long fertility tests, with some males completely infertile and others close to normal fertility

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:222184 )

♂ • seminiferous epithelium is thinner in 3 month old testes and contains numerous vacuoles

small testis ( J:222184 )

♂ • 12 week old males exhibit reduced testis size

decreased testis weight ( J:222184 )

♂ • 12 week old males exhibit reduced testis weight

cellular

abnormal sperm flagellum morphology ( J:222184 )

♂ • epididymal sperm shows a variety of morphological abnormalities in the flagellum including coiled or headless flagellum

coiled sperm flagellum ( J:222184 )

♂

abnormal sperm head morphology ( J:222184 )

♂ • epididymal sperm shows a variety of morphological abnormalities in the sperm head like crooked, round, or bent heads

decreased male germ cell number ( J:222184 )

♂ • seminiferous epithelium is thinner in 3 month old testes and contains numerous vacuoles, indicative of germ cell depletion

♂ • presence of numerous degenerating/degenerated spermatids, or even spermatocytes in the epididymis; this enhanced depletion of spermatocytes and spermatids and the production of deformed spermatozoa are seen only in mice older than 2 months and no differences are seen during the first wave of spermatogenesis

♂ • proportional increase of meiotic cells (i.e.spermatocytes) and decrease in haploid cells (spermatids) despite lowered total cell number in both populations, indicating active depletion of spermatocytes and spermatids

oligozoospermia ( J:222184 )

♂ • sperm counts are lower in 12 week old males

increased male germ cell apoptosis ( J:222184 )

♂ • about 2-fold increase in apoptotic cells, mainly spermatocytes and early round spermatids, in the testes

♂ • seminiferous tubules at around stage VI exhibit round spermatids with an increase in unrepaired DNA double-strand breaks

decreased sperm progressive motility ( J:222184 )

♂

asthenozoospermia ( J:222184 )

♂ • total motility and progressive motility of sperm are reduced in 12 week old males

Genotype
MGI:7356612

cn45

• Allelic Composition: Rbm46^em3Rpc/Rbm46^em3Rpc; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6J * FVB/NJ * SJL/J

reproductive system

small testis ( J:330079 )

♂

decreased testis weight ( J:330079 )

♂

abnormal spermatogenesis ( J:330079 )

♂ • seminiferous epithelia of testes contain only somatic Sertoli cells and a few spermatogonia

endocrine/exocrine glands

small testis ( J:330079 )

♂

decreased testis weight ( J:330079 )

♂

Genotype
MGI:7444373

cn46

• Allelic Composition: Cep250^{tm1a(EUCOMM)Wtsi}/Cep250^{tm1a(EUCOMM)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6N

cellular

decreased male germ cell number ( J:326549 )

♂ • reduction of germ cells was observed in mutant testes at 8 weeks

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:326549 )

♂ • fewer seminiferous tubules are present

small seminiferous tubules ( J:326549 )

♂

small testis ( J:326549 )

♂ • at 8 and 15 weeks of age

reproductive system

decreased male germ cell number ( J:326549 )

♂ • reduction of germ cells was observed in mutant testes at 8 weeks

abnormal seminiferous tubule morphology ( J:326549 )

♂ • fewer seminiferous tubules are present

small seminiferous tubules ( J:326549 )

♂

small testis ( J:326549 )

♂ • at 8 and 15 weeks of age

Genotype
MGI:6274241

cn47

• Allelic Composition: Katnal2^{tm1c(EUCOMM)Wtsi}/Katnal2^{tm1c(EUCOMM)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6N * FVB/NJ
• Cell Lines: EPD0656_4_A03

Spermatogenic defects in Katnal2^{tm1a(EUCOMM)Wtsi}/Katnal2^{tm1a(EUCOMM)Wtsi} Tg(Stra8-icre)1Reb/0 mice

reproductive system

abnormal sperm flagellum morphology ( J:250115 )

♂ • males exhibit a sperm tail phenotype identical to that seen in Katnal2^m1Anu homozygotes

abnormal spermatid morphology ( J:250115 )

♂ • elongating spermatids frequently exhibit abnormal nuclear morphology

elongated manchette ( J:250115 )

♂ • males exhibit a manchette phenotype identical to that seen in Katnal2^m1Anu homozygotes

multinucleated giant male germ cells ( J:250115 )

♂ • multinucleated symplasts are frequently observed in the seminiferous epithelium

abnormal seminiferous tubule epithelium morphology ( J:250115 )

♂ • multinucleated symplasts are frequently observed in the seminiferous epithelium

abnormal spermiation ( J:250115 )

♂ • total epididymal sperm content is reduced by 94.1% relative to control mice; however, testis weight and daily sperm output in the testes are normal, indicating a massive failure of spermiation

♂ • retained elongated spermatids are often observed in stage IX tubules, unlike in control mice

♂ • however, in contrast to Katnal2^m1Anu homozygotes, tubulobulbar complex and residual body formation is similar to that observed in control mice

male infertility ( J:250115 )

♂

cellular

abnormal sperm flagellum morphology ( J:250115 )

♂ • males exhibit a sperm tail phenotype identical to that seen in Katnal2^m1Anu homozygotes

abnormal spermatid morphology ( J:250115 )

♂ • elongating spermatids frequently exhibit abnormal nuclear morphology

elongated manchette ( J:250115 )

♂ • males exhibit a manchette phenotype identical to that seen in Katnal2^m1Anu homozygotes

multinucleated giant male germ cells ( J:250115 )

♂ • multinucleated symplasts are frequently observed in the seminiferous epithelium

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:250115 )

♂ • multinucleated symplasts are frequently observed in the seminiferous epithelium

Genotype
MGI:6156877

cn48

• Allelic Composition: Tdrd5^{tm1c(EUCOMM)Hmgu}/Tdrd5^{tm1c(EUCOMM)Hmgu}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6N * FVB/NJ

endocrine/exocrine glands

decreased testis weight ( J:255733 )

♂ • average 50% reduction

testicular atrophy ( J:255733 )

♂ • average 50% of wild-type weight

reproductive system

decreased testis weight ( J:255733 )

♂ • average 50% reduction

testicular atrophy ( J:255733 )

♂ • average 50% of wild-type weight

arrest of spermatogenesis ( J:255733 )

♂ • at round spermatid stage; no elongating spermatids or spermatozoa formed

male infertility ( J:255733 )

♂

Genotype
MGI:6369095

cn49

• Allelic Composition: Crisp2^{tm1c(KOMP)Mbp}/Crisp2^{tm1c(KOMP)Mbp}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6N * FVB/NJ

reproductive system

reproductive system phenotype ( J:273472 )

♀N • female fertility is similar to controls

decreased sperm progressive motility ( J:273472 )

♂ • significant reduction in the percentage of sperm displaying rapid forms of progressive motility

asthenozoospermia ( J:273472 )

♂ • show a 28.7% reduction in the number of sperm showing any form of motility

reduced male fertility ( J:273472 )

♂ • males are sub-fertile

♂ • however, testes weight and sperm production and histology are similar to controls

impaired acrosome reaction ( J:273472 )

♂ • decrease in the percentage of sperm that undergo progesterone-evoked acrosome reaction

cellular

decreased sperm progressive motility ( J:273472 )

♂ • significant reduction in the percentage of sperm displaying rapid forms of progressive motility

asthenozoospermia ( J:273472 )

♂ • show a 28.7% reduction in the number of sperm showing any form of motility

Genotype
MGI:6690603

cn50

• Allelic Composition: Phf7^{tm1c(EUCOMM)Hmgu}/Phf7^{tm1c(EUCOMM)Hmgu}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6N * FVB/NJ

reproductive system

oligozoospermia ( J:298823 )

♂

abnormal sperm head morphology ( J:298823 )

♂ • globular and larger head with nuclei

globozoospermia ( J:298823 )

♂

abnormal sperm nucleus morphology ( J:298823 )

♂ • less condensed chromatin; defective histone to protamine exchange during spermiogenesis

enlarged sperm head ( J:298823 )

♂

asthenozoospermia ( J:298823 )

♂

male infertility ( J:298823 )

♂

decreased fertilization frequency ( J:298823 )

♂ • during in vitro fertilization

cellular

oligozoospermia ( J:298823 )

♂

abnormal sperm head morphology ( J:298823 )

♂ • globular and larger head with nuclei

globozoospermia ( J:298823 )

♂

abnormal sperm nucleus morphology ( J:298823 )

♂ • less condensed chromatin; defective histone to protamine exchange during spermiogenesis

enlarged sperm head ( J:298823 )

♂

asthenozoospermia ( J:298823 )

♂

Genotype
MGI:6857985

cn51

• Allelic Composition: Ift140^{tm1c(KOMP)Wtsi}/Ift140^{tm1c(KOMP)Wtsi}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6N * FVB/NJ

reproductive system

reproductive system phenotype ( J:285527 )

♂N • males show normal testis size with no significant differences in testis weight and testis/body weight ratio relative to control males

oligozoospermia ( J:285527 )

♂ • sperm count is significantly reduced; only few sperm are found in the lumen of cauda epididymis

teratozoospermia ( J:285527 )

♂ • SEM analysis revealed epididymal sperm with amorphous heads, short/swollen flagella, uneven thickness of flagella, and other distorted shapes

abnormal sperm flagellum morphology ( J:285527 )

♂ • cauda epididymal sperm from 3- to 4-mo-old males display short and/or bent tails

♂ • vacuoles are present at the base of stunted flagella

abnormal outer dense fiber morphology ( J:285527 )

♂ • misplaced ODFs are observed

abnormal sperm axoneme morphology ( J:285527 )

♂ • some sperm lack a 9 + 2 core axoneme structure

♂ • TEM analysis revealed that the few epididymal and testicular sperm recovered show disorganized axoneme microtubule array

abnormal sperm end piece morphology ( J:285527 )

♂ • some sperm display a swollen tail tip

abnormal sperm mitochondrial morphology ( J:285527 )

♂ • misplaced mitochondria components are observed

abnormal sperm fibrous sheath morphology ( J:285527 )

♂ • misplaced fibrous sheath components are observed

kinked sperm flagellum ( J:285527 )

♂

short sperm flagellum ( J:285527 )

♂

abnormal sperm head morphology ( J:285527 )

♂ • amorphous sperm heads are observed

abnormal sperm nucleus morphology ( J:285527 )

♂ • some sperm show disorganized chromatin structure

abnormal spermatid morphology ( J:285527 )

♂ • in round spermatids, IFT20 protein does not appear to attach as tightly to the nuclear membrane as in control spermatids

♂ • IFT27 protein appears to form a large vesicle, not observed in control round spermatids

abnormal manchette morphology ( J:285527 )

♂ • although IFT88 protein is still present in the cytoplasm of spermatocytes and round spermatids, it is absent from the manchette of elongating spermatids and shows abnormal accumulation in the cells at later stages

decreased sperm progressive motility ( J:285527 )

♂ • a small % of sperm exhibit low beating amplitude with limited forward movement; curvilinear velocity is largely reduced

asthenozoospermia ( J:285527 )

♂ • less than 10% of sperm remain motile; however, their motility is significantly weaker than that of control sperm

immotile sperm ( J:285527 )

♂ • >90% of sperm display no mobility

abnormal spermiogenesis ( J:285527 )

♂ • step 16 spermatids are phagocytosed along the basement membrane after stage VIII

♂ • abnormal shapes of the developing spermatid heads appear in stage X

♂ • an excessive accumulation of cytoplasm is observed in elongating spermatids beginning in stage XII

♂ • epididymides contain round bodies of cytoplasm derived from the sloughing of the cytoplasmic lobes and residual bodies

abnormal spermiation ( J:285527 )

♂ • failure of spermiation in stage VIII leading to a reduction of sperm numbers in the cauda epididymis

♂ • only few sperm are detected in the lumen of seminiferous tubules

male infertility ( J:285527 )

♂ • when mated with adult wild-type females for at least 2 months, all 6-wk-old or adult males tested fail to produce offspring, indicating complete male sterility

♂ • however, males show normal sexual behavior and vaginal plug formation

impaired fertilization ( J:285527 )

♂ • in an in vitro fertilization assay, only 5 of 84 C57BL/6J oocytes incubated with mutant sperm progressed to the 2-cell stage; three of these appeared markedly abnormal and none progressed to the 4-cell stage

cellular

oligozoospermia ( J:285527 )

♂ • sperm count is significantly reduced; only few sperm are found in the lumen of cauda epididymis

teratozoospermia ( J:285527 )

♂ • SEM analysis revealed epididymal sperm with amorphous heads, short/swollen flagella, uneven thickness of flagella, and other distorted shapes

abnormal sperm flagellum morphology ( J:285527 )

♂ • cauda epididymal sperm from 3- to 4-mo-old males display short and/or bent tails

♂ • vacuoles are present at the base of stunted flagella

abnormal outer dense fiber morphology ( J:285527 )

♂ • misplaced ODFs are observed

abnormal sperm axoneme morphology ( J:285527 )

♂ • TEM analysis revealed that the few epididymal and testicular sperm recovered show disorganized axoneme microtubule array

♂ • some sperm lack a 9 + 2 core axoneme structure

abnormal sperm end piece morphology ( J:285527 )

♂ • some sperm display a swollen tail tip

abnormal sperm mitochondrial morphology ( J:285527 )

♂ • misplaced mitochondria components are observed

abnormal sperm fibrous sheath morphology ( J:285527 )

♂ • misplaced fibrous sheath components are observed

kinked sperm flagellum ( J:285527 )

♂

short sperm flagellum ( J:285527 )

♂

abnormal sperm head morphology ( J:285527 )

♂ • amorphous sperm heads are observed

abnormal sperm nucleus morphology ( J:285527 )

♂ • some sperm show disorganized chromatin structure

abnormal spermatid morphology ( J:285527 )

♂ • in round spermatids, IFT20 protein does not appear to attach as tightly to the nuclear membrane as in control spermatids

♂ • IFT27 protein appears to form a large vesicle, not observed in control round spermatids

abnormal manchette morphology ( J:285527 )

♂ • although IFT88 protein is still present in the cytoplasm of spermatocytes and round spermatids, it is absent from the manchette of elongating spermatids and shows abnormal accumulation in the cells at later stages

decreased sperm progressive motility ( J:285527 )

♂ • a small % of sperm exhibit low beating amplitude with limited forward movement; curvilinear velocity is largely reduced

asthenozoospermia ( J:285527 )

♂ • less than 10% of sperm remain motile; however, their motility is significantly weaker than that of control sperm

immotile sperm ( J:285527 )

♂ • >90% of sperm display no mobility

Genotype
MGI:6838391

cn52

• Allelic Composition: Cenpv^{tm1c(EUCOMM)Hmgu}/Cenpv^{tm1c(EUCOMM)Hmgu}; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6N * FVB/NJ

reproductive system

impaired polar body extrusion ( J:314905 )

♀ • decrease in polar body extrusion

cellular

impaired polar body extrusion ( J:314905 )

♀ • decrease in polar body extrusion

Genotype
MGI:5904161

cn53

• Allelic Composition: Tg(Stra8-icre)1Reb/0; Zscan21^tm1.1Jiwa/Zscan21^tm1.1Jiwa
• Genetic Background: involves: FVB/NJ

reproductive system

abnormal spermatid morphology ( J:237046 )

♂ • testes show no round spermatids

abnormal spermatocyte morphology ( J:237046 )

♂ • testes show few spermatocytes, without round spermatids

abnormal X-Y chromosome synapsis during male meiosis ( J:237046 )

♂ • unsynapsed or partially synapsed chromosomes are seen in spermatocytes indicating failure of chromosomal synapsis

arrest of male meiosis ( J:237046 )

♂ • spermatocytes do not progress to meiotic prophase I

decreased testis weight ( J:237046 )

♂ • testis weight of adult males is less than 40% of heterozygotes

male infertility ( J:237046 )

♂ • males are infertile, with 6-8 week old males failing to produce offspring after natural mating with wild-type females for more than 4 months

cellular

abnormal spermatid morphology ( J:237046 )

♂ • testes show no round spermatids

abnormal spermatocyte morphology ( J:237046 )

♂ • testes show few spermatocytes, without round spermatids

abnormal X-Y chromosome synapsis during male meiosis ( J:237046 )

♂ • unsynapsed or partially synapsed chromosomes are seen in spermatocytes indicating failure of chromosomal synapsis

arrest of male meiosis ( J:237046 )

♂ • spermatocytes do not progress to meiotic prophase I

abnormal double-strand DNA break repair ( J:237046 )

♂ • failure of double-strand DNA break repair in spermatocytes as indicated by reduced MLH1 foci and RAD51 foci

endocrine/exocrine glands

decreased testis weight ( J:237046 )

♂ • testis weight of adult males is less than 40% of heterozygotes

homeostasis/metabolism

abnormal double-strand DNA break repair ( J:237046 )

♂ • failure of double-strand DNA break repair in spermatocytes as indicated by reduced MLH1 foci and RAD51 foci

Genotype
MGI:5763275

cn54

• Allelic Composition: Tg(RNU6-RNAi:Rhox3)2Wilk/0; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: FVB/NJ

reproductive system

abnormal spermatid morphology ( J:229199 )

♂ • abnormal of elongated spermatids

decreased male germ cell number ( J:229199 )

♂

oligozoospermia ( J:229199 )

♂ • few sperm in the cauda epididymides (greater than 100 fold reduction)

abnormal male meiosis ( J:229199 )

♂ • defective meiotic prophase

increased male germ cell apoptosis ( J:229199 )

♂ • of pachytene spermatocyte in seminiferous epithelial cycle stage IV

♂ • of spermatocytes undergoing meiotic metaphase in stage XII

♂ • of abnormal elongated spermatids

small seminiferous tubules ( J:229199 )

♂ • decreased diameter

decreased testis weight ( J:229199 )

♂ • however, seminal vesicle weight is normal

male infertility ( J:229199 )

♂

cellular

abnormal spermatid morphology ( J:229199 )

♂ • abnormal of elongated spermatids

decreased male germ cell number ( J:229199 )

♂

oligozoospermia ( J:229199 )

♂ • few sperm in the cauda epididymides (greater than 100 fold reduction)

abnormal male meiosis ( J:229199 )

♂ • defective meiotic prophase

increased male germ cell apoptosis ( J:229199 )

♂ • of pachytene spermatocyte in seminiferous epithelial cycle stage IV

♂ • of spermatocytes undergoing meiotic metaphase in stage XII

♂ • of abnormal elongated spermatids

endocrine/exocrine glands

small seminiferous tubules ( J:229199 )

♂ • decreased diameter

decreased testis weight ( J:229199 )

♂ • however, seminal vesicle weight is normal

Genotype
MGI:7507026

cn55

• Allelic Composition: Cxxc1^tm2.1Skk/Cxxc1^tm2.1Skk; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: FVB/NJ

reproductive system

reproductive system phenotype ( J:329283 )

♂N • at 11 weeks of age, seminal vesicles, prostate, vas deferens and epididymis appear normal

abnormal spermatogonia morphology ( J:329283 )

♂ • number of spermatogonial cells is modestly increased

decreased male germ cell number ( J:329283 )

♂ • marked depletion of germ cells starting at 3 weeks of age

abnormal chromosomal synapsis ( J:329283 )

♂ • spermatogonia enter the first stage of the meiotic process but fail to form synapsed homologous chromosomes during pachynema

♂ • relative number of normal synapsed chromosomes is significantly reduced

increased male germ cell apoptosis ( J:329283 )

♂ • significant increase of TUNEL+ male germ cells in the seminiferous tubules at 3 and 4 weeks, but not at 2 weeks, of age

abnormal seminiferous tubule morphology ( J:329283 )

♂ • at 6 weeks of age, most seminiferous tubules contain only spermatogonia, few spermatocytes and spermatids, and Sertoli cells

decreased testis weight ( J:329283 )

♂ • significant reduction in testis weight/body weight (g) at 6 and 11 weeks of age

testis hypoplasia ( J:329283 )

♂ • testis hypoplasia at 11 weeks of age

abnormal spermatogenesis ( J:329283 )

♂ • although spermatogonia and spermatocytes are present at P18, only few or no spermatids are detected in the seminiferous tubules at 6 weeks of age

azoospermia ( J:329283 )

♂ • no mature sperm are detected in the lumen of the epididymis at 6 weeks of age

abnormal acrosome morphology ( J:329283 )

♂ • at 6 weeks of age, immunofluorescence with PNA (which labels the acrosomal cap of spermatids and spermatozoa) showed a small dot-like pattern, unlike the crescent-like pattern seen in control spermatids

arrest of spermatogenesis ( J:329283 )

♂ • flow cytometric analysis showed that one chromatid per chromosome (1C)-containing germ cells (round spermatids) are markedly reduced (13.43% vs. 4.20% in controls), whereas 4C (meiocytes in prophase I) and 2C [spermatogonia and secondary spermatocytes (MII)] germ cells are not grossly altered

♂ • pachynema, diplonema, and MII are significantly decreased

♂ • Cenpa staining suggests that pachynemas showing incomplete centromere pairing are eliminated as their numbers at diplotene are reduced

arrest of male meiosis ( J:329283 )

♂ • failure in prophase I of the first meiosis; complete meiotic arrest is due to reduced expression of meiotic genes and reduced homologous recombination process

male infertility ( J:329283 )

♂ • male mice fail to produce pups when mated with wild-type female mice for over 6 months

cellular

abnormal acrosome morphology ( J:329283 )

♂ • at 6 weeks of age, immunofluorescence with PNA (which labels the acrosomal cap of spermatids and spermatozoa) showed a small dot-like pattern, unlike the crescent-like pattern seen in control spermatids

abnormal spermatogonia morphology ( J:329283 )

♂ • number of spermatogonial cells is modestly increased

decreased male germ cell number ( J:329283 )

♂ • marked depletion of germ cells starting at 3 weeks of age

azoospermia ( J:329283 )

♂ • no mature sperm are detected in the lumen of the epididymis at 6 weeks of age

abnormal chromosomal synapsis ( J:329283 )

♂ • spermatogonia enter the first stage of the meiotic process but fail to form synapsed homologous chromosomes during pachynema

♂ • relative number of normal synapsed chromosomes is significantly reduced

arrest of male meiosis ( J:329283 )

♂ • failure in prophase I of the first meiosis; complete meiotic arrest is due to reduced expression of meiotic genes and reduced homologous recombination process

increased male germ cell apoptosis ( J:329283 )

♂ • significant increase of TUNEL+ male germ cells in the seminiferous tubules at 3 and 4 weeks, but not at 2 weeks, of age

abnormal epigenetic regulation of gene expression ( J:329283 )

♂ • H3K4me3 levels at transcription start sites (TSSs) and CpG islands (CGIs) are diminished in spermatocytes

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:329283 )

♂ • at 6 weeks of age, most seminiferous tubules contain only spermatogonia, few spermatocytes and spermatids, and Sertoli cells

decreased testis weight ( J:329283 )

♂ • significant reduction in testis weight/body weight (g) at 6 and 11 weeks of age

testis hypoplasia ( J:329283 )

♂ • testis hypoplasia at 11 weeks of age

Genotype
MGI:3850155

tg56

• Allelic Composition: Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: FVB

normal phenotype

no abnormal phenotype detected ( J:148746 )

• mice are viable and fertile; no phenotypic details are provided