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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Ddx4-cre)1Dcas
transgene insertion 1, Diego H Castrillon
MGI:3757577
Summary 33 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
G3bp2em1Smoc/G3bp2em1.1Smoc
Tg(Ddx4-cre)1Dcas/0
B6.Cg-G3bp2em1Smoc/G3bp2em1.1Smoc Tg(Ddx4-cre)1Dcas MGI:7333231
cn2
Bscl2tm1.1Gliu/Bscl2tm1.1Gliu
Tg(Ddx4-cre)1Dcas/0
involves: 129 * 129S4/SvJaeSor * FVB/N MGI:5629953
cn3
Pum1tm1.1Hfl/Pum1tm1.2Hfl
Tg(Ddx4-cre)1Dcas/0
involves: 129 * C57BL/6 * FVB MGI:5316380
cn4
Lancl1tm1Pfw/Lancl1tm1.1Pfw
Tg(Ddx4-cre)1Dcas/0
involves: 129 * C57BL/6 * FVB MGI:7294208
cn5
Elp1tm1c(KOMP)Wtsi/Elp1tm1c(KOMP)Wtsi
Tg(Ddx4-cre)1Dcas/0
involves: 129 * C57BL/6N * FVB MGI:7509348
cn6
Aurkatm1.1Tvd/Aurkatm1.1Tvd
Tg(Ddx4-cre)1Dcas/0
involves: 129P2/OlaHsd * C57BL/6J * FVB MGI:7287842
cn7
Tg(Ddx4-cre)1Dcas/0
Uxttm1.1Sklo/Y
involves: 129S1/Sv * C57BL/6 * FVB MGI:6159374
cn8
Tsc22d3tm1.1Hum/Y
Tg(Ddx4-cre)1Dcas/0
involves: 129S1/SvImJ * C57BL/6N * FVB MGI:5700201
cn9
Tg(Ddx4-cre)1Dcas/0
Tg(EIF1AX-Lin28a)#Gqda/0
involves: 129S4/SvJae * C57BL/6 * CD-1 * FVB/N MGI:5638792
cn10
Skp1tm1.1Jw/Skp1tm1.2Jw
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJae * C57BL/6 * FVB MGI:6455745
cn11
Ythdc1tm1.1Jw/Ythdc1tm1.2Jw
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJae * C57BL/6 * FVB MGI:6194789
cn12
Nxf2tm1.1JwNxf3tm1.1Jw/Y
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJae * C57BL/6 * FVB MGI:5500935
cn13
Ptentm1Hwu/Ptentm1Hwu
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJae * FVB/N MGI:4882148
cn14
Mettl3tm1.1Jhha/Mettl3tm1.1Jhha
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJaeSor * BALB/c * C57BL/6 * FVB MGI:6491898
cn15
Ddx6em1.1Ysa/Ddx6em1.1Ysa
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJaeSor * C57BL/6NCrlj * CBA/JNCrlj * FVB MGI:7526270
cn16
Sox30tm1c(KOMP)Wtsi/Sox30tm1c(KOMP)Wtsi
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJaeSor * C57BL/6N * FVB MGI:6115516
cn17
Meioctm1c(KOMP)Wtsi/Meioctm1c(KOMP)Wtsi
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJaeSor * C57BL/6N * FVB MGI:5897828
cn18
Hdac8tm1.1Eno/Hdac8tm1.2Eno
Tg(Ddx4-cre)1Dcas/0
involves: 129S6/SvEvTac * C57BL/6J * FVB MGI:6835645
cn19
Foxo3tm1Rdp/Foxo3tm1Rdp
Tg(Ddx4-cre)1Dcas/0
involves: 129S6/SvEvTac * FVB/N MGI:4882147
cn20
Spata31tm1Yangy/Spata31tm1Yangy
Tg(Ddx4-cre)1Dcas/0
involves: 129S7/SvEvBrd * FVB MGI:6510016
cn21
Hsp90b1tm1Zhli/Hsp90b1tm1.1Zhli
Tg(Ddx4-cre)1Dcas/0
involves: 129S/SvEv * FVB MGI:6885740
cn22
Tsc22d3tm1Ric/Y
Tg(Ddx4-cre)1Dcas/?
involves: C57BL/6 * FVB MGI:5308362
cn23
Gt(ROSA)26Sortm2(CAG-Lancl1)Pfw/Gt(ROSA)26Sor+
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6 * FVB MGI:7294209
cn24
Tg(Ddx4-cre)1Dcas/0
Rnf220em1Kust/Rnf220em1Kust
involves: C57BL/6 * FVB MGI:6451400
cn25
Mettl3em1Chhe/Mettl3em1Chhe
Mettl14em1Chhe/Mettl14em1Chhe
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6J * FVB MGI:6681848
cn26
Rad51tm1Csha/Rad51tm1Csha
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6J * FVB MGI:7311694
cn27
Mettl3em1Chhe/Mettl3em1Chhe
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6J * FVB MGI:6681844
cn28
Mettl14em1Chhe/Mettl14em1Chhe
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6J * FVB MGI:6681845
cn29
Ppp2catm1.1Jmli/Ppp2catm1.2Jmli
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6J * FVB MGI:5795985
cn30
Cenpvtm1c(EUCOMM)Hmgu/Cenpvtm1c(EUCOMM)Hmgu
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6N * FVB MGI:6838392
cn31
Ddx5tm1.1Arte/Ddx5tm1.1Arte
Tg(Ddx4-cre)1Dcas/0
involves: C57BL/6NTac * FVB MGI:7287664
cn32
Foxj2tm1.1Mxc/Foxj2tm1.1Mxc
Tg(Ddx4-cre)1Dcas/0
involves: FVB MGI:6693629
cn33
Usp9xtm1Tuv/Y
Tg(Ddx4-cre)1Dcas/0
involves: FVB MGI:7285921


Genotype
MGI:7333231
cn1
Allelic
Composition
G3bp2em1Smoc/G3bp2em1.1Smoc
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
B6.Cg-G3bp2em1Smoc/G3bp2em1.1Smoc Tg(Ddx4-cre)1Dcas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
G3bp2em1.1Smoc mutation (0 available); any G3bp2 mutation (60 available)
G3bp2em1Smoc mutation (0 available); any G3bp2 mutation (60 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• male mice exhibit normal spermatogenesis and fertility

cellular




Genotype
MGI:5629953
cn2
Allelic
Composition
Bscl2tm1.1Gliu/Bscl2tm1.1Gliu
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129 * 129S4/SvJaeSor * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bscl2tm1.1Gliu mutation (0 available); any Bscl2 mutation (36 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• oligoasthenoteratozoospermia
• lower percentage of motile sperm
• testes contain many degenerating masses composed of fragmented spermatids and large lipid droplets
• testes contains prominent bundles of two or more interconnected sperm
• lower sperm counts
• cauda epididymides are almost entirely devoid of sperm but contain numerous spherical cells
• sperm is morphologically abnormal, with 18% of sperm showing head and tail abnormalities compared to 6% of controls
• tail defects include folded sperm or sheath abnormalities
• defects in sperm heads include lack of the usual hook and banana-like or amorphous forms
• some sperm exhibit cavities in the sperm head
• the numbers of spermatocytes in stages VII and VII seminiferous tubules are similar to wild-type mice, but tubules contain fewer round spermatids, indicating loss of round spermatids
• presence of large ectopic lipid droplets in round, elongating and elongated spermatids
• spermatids exhibit defects in chromatin condensation
• males exhibit structural defects in late spermiogenesis; abnormal clustering of late spermatids of seminiferous tubules at stages VII and VIII of the seminiferous epithelial cycle , with the heads of these spermatids randomly oriented instead of being aligned perpendicular to the seminiferous tubule basement membrane
• seminiferous tubule sections near completion of spermiogenesis contain massive accumulations of spermatids in bundle-like structures
• males exhibit normal mating behavior, however, no pregnancies or offspring are seen in breeding pairs of wild-type females and mutant males
• however, males show normal serum FSH, LH, testosterone and estradiol levels

cellular
• oligoasthenoteratozoospermia
• lower sperm counts
• cauda epididymides are almost entirely devoid of sperm but contain numerous spherical cells
• sperm is morphologically abnormal, with 18% of sperm showing head and tail abnormalities compared to 6% of controls
• tail defects include folded sperm or sheath abnormalities
• defects in sperm heads include lack of the usual hook and banana-like or amorphous forms
• some sperm exhibit cavities in the sperm head
• the numbers of spermatocytes in stages VII and VII seminiferous tubules are similar to wild-type mice, but tubules contain fewer round spermatids, indicating loss of round spermatids
• presence of large ectopic lipid droplets in round, elongating and elongated spermatids
• spermatids exhibit defects in chromatin condensation
• lower percentage of motile sperm

endocrine/exocrine glands
• testes contain many degenerating masses composed of fragmented spermatids and large lipid droplets

homeostasis/metabolism
N
• males exhibit normal fasting plasma levels of cholesterol, triglycerides, and glucose and normal serum levels of insulin in a fed state
• the relative content of phosphatidic acid is 46% higher in the testis
• elevation of phosphatidylinositol levels in the testis
• higher ratios of phosphatidic acid to phosphatidylcholine and of phosphatidic acid to phospholipid in the testis

adipose tissue
N
• normal levels of adipose tissue




Genotype
MGI:5316380
cn3
Allelic
Composition
Pum1tm1.1Hfl/Pum1tm1.2Hfl
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129 * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pum1tm1.1Hfl mutation (0 available); any Pum1 mutation (169 available)
Pum1tm1.2Hfl mutation (0 available); any Pum1 mutation (169 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• 7.5-fold higher than in control mice

cellular
• 7.5-fold higher than in control mice




Genotype
MGI:7294208
cn4
Allelic
Composition
Lancl1tm1Pfw/Lancl1tm1.1Pfw
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129 * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lancl1tm1.1Pfw mutation (0 available); any Lancl1 mutation (21 available)
Lancl1tm1Pfw mutation (0 available); any Lancl1 mutation (21 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at 8 weeks of age, the number of ACRV1+ germ cells (spermatids and spermatozoa) per tubule is significantly lower than that in control testes; the protein level of acrosin (an acrosome marker) is reduced
• at 8 weeks of age, testis weight-to-body weight ratio is significantly lower than that in control males
• however, body weight is normal
• at 8 weeks of age, seminiferous tubules show obvious spermatogenic defects and a lower Johnsen's score, similar to Lancl1tm1.1Pfw homozygous males
• at 8 weeks of age, caudal epididymal sperm concentration is significantly lower than that in control males
• spermatozoa exhibit significantly increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, indicating oxidative stress
• at 8 weeks of age, sperm forward motility (%) is significantly lower than that in control males
• at 8 weeks of age, sperm motility (%) is significantly lower than that in control males

cellular
• at 8 weeks of age, the number of ACRV1+ germ cells (spermatids and spermatozoa) per tubule is significantly lower than that in control testes; the protein level of acrosin (an acrosome marker) is reduced
• at 8 weeks of age, caudal epididymal sperm concentration is significantly lower than that in control males
• at 8 weeks of age, sperm forward motility (%) is significantly lower than that in control males
• at 8 weeks of age, sperm motility (%) is significantly lower than that in control males
• spermatozoa exhibit significantly increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, indicating oxidative stress
• at 8 weeks of age, testes show an increased number of gammaH2AX+ cells in the seminiferous tubules and increased protein levels of 4-hydroxy-2-nonenal (4-HNE) and BAX, indicating oxidative damage in maturing male germ cells

endocrine/exocrine glands
• at 8 weeks of age, testis weight-to-body weight ratio is significantly lower than that in control males
• however, body weight is normal




Genotype
MGI:7509348
cn5
Allelic
Composition
Elp1tm1c(KOMP)Wtsi/Elp1tm1c(KOMP)Wtsi
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129 * C57BL/6N * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Elp1tm1c(KOMP)Wtsi mutation (0 available); any Elp1 mutation (69 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• impairment of meiotic progression in male germ cells takes place between zygotene to pachytene stage

homeostasis/metabolism

endocrine/exocrine glands
• testicular weight to body weight ratio was reduced by 25% at the age of 14 month

reproductive system
• impairment of meiotic progression in male germ cells takes place between zygotene to pachytene stage
• testicular weight to body weight ratio was reduced by 25% at the age of 14 month




Genotype
MGI:7287842
cn6
Allelic
Composition
Aurkatm1.1Tvd/Aurkatm1.1Tvd
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aurkatm1.1Tvd mutation (1 available); any Aurka mutation (40 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• cauda epididymides are devoid of sperm
• males show absence of all developing germ cells in the testis, presumably due to a block in mitosis
• seminiferous tubules lack germ cells and exhibit Sertoli cell-only phenotype
• spermatogonia are eliminated, only Sertoli cells are detected in the seminiferous epithelium
• testes are significantly smaller than those in control males
• cauda epididymides are devoid of sperm
• however, cauda epididymis weight is normal

cellular
• cauda epididymides are devoid of sperm
• males show absence of all developing germ cells in the testis, presumably due to a block in mitosis

endocrine/exocrine glands
• seminiferous tubules lack germ cells and exhibit Sertoli cell-only phenotype
• spermatogonia are eliminated, only Sertoli cells are detected in the seminiferous epithelium
• testes are significantly smaller than those in control males




Genotype
MGI:6159374
cn7
Allelic
Composition
Tg(Ddx4-cre)1Dcas/0
Uxttm1.1Sklo/Y
Genetic
Background
involves: 129S1/Sv * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ddx4-cre)1Dcas mutation (2 available)
Uxttm1.1Sklo mutation (0 available); any Uxt mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• contain on average 1.5 times more cleaved caspase-3 positive tubules at 7 days post-partum compared to controls
• however, the number of apoptotic cells per tubule is similar to controls
• display a Sertoli cell only syndrome
• at 5 months of age
• at 5 months of age
• all germ cells are lost during the first wave of spermatogenesis
• loss of germ cells and absence of sperm in the epididymis
• Sertoli cell only syndrome develops by 23 days post-partum
• expression analysis indicates misregulation of some differentiation pathways during the first wave of spermatogenesis
• cells do not leave the basement membrane and fail to develop past the leptotene stage

endocrine/exocrine glands
• display a Sertoli cell only syndrome
• at 5 months of age
• at 5 months of age

cellular
• loss of germ cells and absence of sperm in the epididymis
• Sertoli cell only syndrome develops by 23 days post-partum
• expression analysis indicates misregulation of some differentiation pathways during the first wave of spermatogenesis
• cells do not leave the basement membrane and fail to develop past the leptotene stage
• contain on average 1.5 times more cleaved caspase-3 positive tubules at 7 days post-partum compared to controls
• however, the number of apoptotic cells per tubule is similar to controls




Genotype
MGI:5700201
cn8
Allelic
Composition
Tsc22d3tm1.1Hum/Y
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S1/SvImJ * C57BL/6N * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ddx4-cre)1Dcas mutation (2 available)
Tsc22d3tm1.1Hum mutation (0 available); any Tsc22d3 mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• disorganized seminiferous epithelium

reproductive system
• when expression is disrupted specifically in the male germ cells, hemizygous males have the spermatogenesis failure, sterility, small testis and disrupted seminiferous epithelium as hemizygous null males
• disorganized seminiferous epithelium
• complete male sterility

cellular
• when expression is disrupted specifically in the male germ cells, hemizygous males have the spermatogenesis failure, sterility, small testis and disrupted seminiferous epithelium as hemizygous null males




Genotype
MGI:5638792
cn9
Allelic
Composition
Tg(Ddx4-cre)1Dcas/0
Tg(EIF1AX-Lin28a)#Gqda/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ddx4-cre)1Dcas mutation (2 available)
Tg(EIF1AX-Lin28a)#Gqda mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• perinatal lethality is seen in offspring from crosses between Tg(EIF1AX-Lin28a)#Gqda males with Tg(Ddx4-cre)1Dcas females (cre is expressed in oocytes)

neoplasm
• 10% of offspring from crosses between Tg(EIF1AX-Lin28a)#Gqda females with Tg(Ddx4-cre)1Dcas males (cre is expressed in primordial germ cells) develop renal tumors resembling Wilms tumor
• kidneys from E18.5 mutants transplanted under the kidney capsule of immunodeficient mice results in tumor development similar to Wilms tumor

renal/urinary system
• kidneys are larger at E18.5
• 10% of offspring from crosses between Tg(EIF1AX-Lin28a)#Gqda females with Tg(Ddx4-cre)1Dcas males (cre is expressed in primordial germ cells) develop renal tumors resembling Wilms tumor
• kidneys from E18.5 mutants transplanted under the kidney capsule of immunodeficient mice results in tumor development similar to Wilms tumor
• persistent proliferation of cap mesenchyme cells in adults
• timing of kidney development is prolonged, sustaining proliferation of the cap mesenchyme cells into adulthood
• E18.5 kidneys contain fewer mature proximal tubules

growth/size/body
• kidneys are larger at E18.5

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
nephroblastoma DOID:2154 OMIM:194070
J:211179




Genotype
MGI:6455745
cn10
Allelic
Composition
Skp1tm1.1Jw/Skp1tm1.2Jw
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Skp1tm1.1Jw mutation (0 available); any Skp1 mutation (18 available)
Skp1tm1.2Jw mutation (0 available); any Skp1 mutation (18 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular

reproductive system




Genotype
MGI:6194789
cn11
Allelic
Composition
Ythdc1tm1.1Jw/Ythdc1tm1.2Jw
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ddx4-cre)1Dcas mutation (2 available)
Ythdc1tm1.1Jw mutation (1 available); any Ythdc1 mutation (51 available)
Ythdc1tm1.2Jw mutation (0 available); any Ythdc1 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• oocytes contain cytoplasmic RNA granules unlike in oocytes from control mice
• at 6 months of age and beyond
• lack of germ cells at PND25 and in adult male mice
• fewer spermatogonia in seminiferous tubules at PND8 compared with control mice
• ovaries lack secondary follicles
• ovaries lack antral follicles
• blocked at the primary follicle stage

endocrine/exocrine glands
• ovaries lack secondary follicles
• ovaries lack antral follicles
• blocked at the primary follicle stage

cellular
• oocytes contain cytoplasmic RNA granules unlike in oocytes from control mice
• at 6 months of age and beyond
• lack of germ cells at PND25 and in adult male mice
• fewer spermatogonia in seminiferous tubules at PND8 compared with control mice
• oocytes exhibit widespread m6A-dependent-splicing defects and extensive alternative polyadenylation




Genotype
MGI:5500935
cn12
Allelic
Composition
Nxf2tm1.1JwNxf3tm1.1Jw/Y
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nxf2tm1.1Jw mutation (1 available); any Nxf2 mutation (4 available)
Nxf3tm1.1Jw mutation (1 available); any Nxf3 mutation (8 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype



Genotype
MGI:4882148
cn13
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJae * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (16 available); any Pten mutation (88 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• ovaries are enlarged by P21 due to global primordial follicle activation
• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls

reproductive system
• ovaries are enlarged by P21 due to global primordial follicle activation
• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls
• females exhibit a dramatic age-dependent decrease in fertility and have no more than two litters

growth/size/body
• ovaries are enlarged by P21 due to global primordial follicle activation




Genotype
MGI:6491898
cn14
Allelic
Composition
Mettl3tm1.1Jhha/Mettl3tm1.1Jhha
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJaeSor * BALB/c * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mettl3tm1.1Jhha mutation (0 available); any Mettl3 mutation (42 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• massive reduction in testis volume
• severe degeneration

reproductive system
• massive reduction in testis volume
• severe degeneration




Genotype
MGI:7526270
cn15
Allelic
Composition
Ddx6em1.1Ysa/Ddx6em1.1Ysa
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJaeSor * C57BL/6NCrlj * CBA/JNCrlj * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ddx6em1.1Ysa mutation (0 available); any Ddx6 mutation (61 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• adult ovaries lack oocytes
• newborn ovaries show severely impaired assembly of P-body-like granules; the mean area of DCP1A foci is reduced to 15% of that in control ovaries; however, ELAVL2 is robustly expressed in oocytes
• immunostaining of CDH1 (an oocyte marker) together with LAMININ showed direct connection between oocytes, indicating that cyst breakdown is severely impaired
• no nuclear translocation of FOXO3A is observed at P1; instead FOXO3A remains in the cytoplasm of P7 ovaries indicating that PI3K-AKT signaling is abnormally activated
• at P7 and P21, the number of growing follicles, including follicles in the transition state, primary follicles and secondary follicles, is significantly lower than that in control ovaries
• at P7 and P21, the number of primary ovarian follicles is severely reduced
• at P7 and P21, the number of secondary ovarian follicles is severely reduced
• at P21, the number of antral follicles is severely reduced
• at P7, approximately half of the oocytes remain in cysts, unlike in control ovaries where most oocytes have developed to primordial follicles
• at P14, primordial follicles appear abnormally enlarged; the diameter of oocytes in primordial follicles is increased 1.3-fold
• although cyst breakdown is compromised, a substantial number of primordial follicles is detected at P7
• at P21, the number of primordial follicles is severely reduced
• no pups are born when female mice are crossed with wild-type males from 6 to 24 weeks after birth

cellular
• adult ovaries lack oocytes

endocrine/exocrine glands
• newborn ovaries show severely impaired assembly of P-body-like granules; the mean area of DCP1A foci is reduced to 15% of that in control ovaries; however, ELAVL2 is robustly expressed in oocytes
• immunostaining of CDH1 (an oocyte marker) together with LAMININ showed direct connection between oocytes, indicating that cyst breakdown is severely impaired
• no nuclear translocation of FOXO3A is observed at P1; instead FOXO3A remains in the cytoplasm of P7 ovaries indicating that PI3K-AKT signaling is abnormally activated
• at P7 and P21, the number of growing follicles, including follicles in the transition state, primary follicles and secondary follicles, is significantly lower than that in control ovaries
• at P7 and P21, the number of primary ovarian follicles is severely reduced
• at P7 and P21, the number of secondary ovarian follicles is severely reduced
• at P21, the number of antral follicles is severely reduced
• at P7, approximately half of the oocytes remain in cysts, unlike in control ovaries where most oocytes have developed to primordial follicles
• at P14, primordial follicles appear abnormally enlarged; the diameter of oocytes in primordial follicles is increased 1.3-fold
• although cyst breakdown is compromised, a substantial number of primordial follicles is detected at P7
• at P21, the number of primordial follicles is severely reduced




Genotype
MGI:6115516
cn16
Allelic
Composition
Sox30tm1c(KOMP)Wtsi/Sox30tm1c(KOMP)Wtsi
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJaeSor * C57BL/6N * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sox30tm1c(KOMP)Wtsi mutation (0 available); any Sox30 mutation (19 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• multinucleated giant cells are present in the testis cords
• arrest at the round spermatid stage

cellular
• multinucleated giant cells are present in the testis cords




Genotype
MGI:5897828
cn17
Allelic
Composition
Meioctm1c(KOMP)Wtsi/Meioctm1c(KOMP)Wtsi
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S4/SvJaeSor * C57BL/6N * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Meioctm1c(KOMP)Wtsi mutation (0 available); any Meioc mutation (38 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype



Genotype
MGI:6835645
cn18
Allelic
Composition
Hdac8tm1.1Eno/Hdac8tm1.2Eno
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6J * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hdac8tm1.1Eno mutation (0 available); any Hdac8 mutation (10 available)
Hdac8tm1.2Eno mutation (0 available); any Hdac8 mutation (10 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• females exhibit normal ovarian histology and follicle counts at 18 days (prepubertal) and at 7 months of age, indicating normal folliculogenesis
• reduced female fertility is likely due to subtle defects in oogenesis resulting in smaller oocytes with compromised cytoplasmic competence
• fully grown oocytes from hyperstimulated females are significantly smaller than control oocytes, as determined by germinal vesicle diameter
• in vitro oocyte maturation (IVM) analysis revealed that only 80% of germinal vesicle-intact oocytes arrested in prophase of meiosis I are able to resume meiosis and reach metaphase of meiosis I (MI) within 8 h relative to ~90% in controls
• however, spindle morphology and chromosome alignment are normal at the MI stage and no chromosome segregation defects are observed following IVM
• females show a mild subfertility phenotype
• when bred with wild type male mice for 6 months, adult females produce a significantly lower average litter size than controls

cellular
• reduced female fertility is likely due to subtle defects in oogenesis resulting in smaller oocytes with compromised cytoplasmic competence
• fully grown oocytes from hyperstimulated females are significantly smaller than control oocytes, as determined by germinal vesicle diameter
• in vitro oocyte maturation (IVM) analysis revealed that only 80% of germinal vesicle-intact oocytes arrested in prophase of meiosis I are able to resume meiosis and reach metaphase of meiosis I (MI) within 8 h relative to ~90% in controls
• however, spindle morphology and chromosome alignment are normal at the MI stage and no chromosome segregation defects are observed following IVM

embryo
N
• in culture, the % of zygotes progressing to the blastocyst stage is not significantly different from that in controls, suggesting normal preimplantation embryo development




Genotype
MGI:4882147
cn19
Allelic
Composition
Foxo3tm1Rdp/Foxo3tm1Rdp
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo3tm1Rdp mutation (1 available); any Foxo3 mutation (51 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• global primordial follicle activation
• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls

reproductive system
• global primordial follicle activation
• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls

growth/size/body




Genotype
MGI:6510016
cn20
Allelic
Composition
Spata31tm1Yangy/Spata31tm1Yangy
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S7/SvEvBrd * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Spata31tm1Yangy mutation (0 available); any Spata31 mutation (31 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at 8 and 12 weeks of age
• aberrant spermatogenic cells are seen starting at 6 weeks of age
• few elongated spermatids are seen at 8 weeks of age
• by 12 weeks of age round spermatids are nearly absent
• testes size gradually decreases with age and by 12 weeks of age testes are significantly smaller compared to wild-type controls
• premature release of germ cells from the seminiferous epithelium
• males are infertile despite displaying normal mating behavior

cellular
• at 8 and 12 weeks of age
• aberrant spermatogenic cells are seen starting at 6 weeks of age
• few elongated spermatids are seen at 8 weeks of age
• by 12 weeks of age round spermatids are nearly absent

endocrine/exocrine glands
• testes size gradually decreases with age and by 12 weeks of age testes are significantly smaller compared to wild-type controls




Genotype
MGI:6885740
cn21
Allelic
Composition
Hsp90b1tm1Zhli/Hsp90b1tm1.1Zhli
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: 129S/SvEv * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hsp90b1tm1.1Zhli mutation (0 available); any Hsp90b1 mutation (35 available)
Hsp90b1tm1Zhli mutation (0 available); any Hsp90b1 mutation (35 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• adult males show normal testis weight-to-body weight ratio relative to control males
• fluorescent HSPA5 (an ER chaperone) and TO-PRO-3 (DNA) staining revealed strong HSPA5 localization within the abnormal sperm head rather than at the level of the intermediate piece as observed in wild-type sperm
• streptavidin-FITC (biotinylated proteins in mitochondria) and TO-PRO-3 (DNA) staining revealed a stronger streptavidin-FITC labeling concentrated at the abnormal sperm head, unlike in wild-type sperm
• all cauda epididymal sperm show head distortions including abnormal heads with (i) a rather elongated head, ii) a rounded-globular head, and iii) an enlarged-deformed head
• 86% of abnormal sperm heads include types (ii) and (iii)
• normal hook-shaped sperm heads are never observed
• fluorescent Lens culinaris agglutinin (LCA)-fluorescein isothiocyanate (FITC) (glycoconjugates) and TO-PRO-3 (DNA) staining revealed a diffuse and variable labeling of the acrosome, unlike in wild-type sperm
• ~40% of sperm heads are rounded-globular
• ~40% of sperm heads are enlarged and deformed
• cauda epididymal sperm are almost immobile
• adult males are infertile
• however, mating behavior is normal

cellular
• fluorescent HSPA5 (an ER chaperone) and TO-PRO-3 (DNA) staining revealed strong HSPA5 localization within the abnormal sperm head rather than at the level of the intermediate piece as observed in wild-type sperm
• streptavidin-FITC (biotinylated proteins in mitochondria) and TO-PRO-3 (DNA) staining revealed a stronger streptavidin-FITC labeling concentrated at the abnormal sperm head, unlike in wild-type sperm
• all cauda epididymal sperm show head distortions including abnormal heads with (i) a rather elongated head, ii) a rounded-globular head, and iii) an enlarged-deformed head
• 86% of abnormal sperm heads include types (ii) and (iii)
• normal hook-shaped sperm heads are never observed
• fluorescent Lens culinaris agglutinin (LCA)-fluorescein isothiocyanate (FITC) (glycoconjugates) and TO-PRO-3 (DNA) staining revealed a diffuse and variable labeling of the acrosome, unlike in wild-type sperm
• ~40% of sperm heads are rounded-globular
• ~40% of sperm heads are enlarged and deformed
• cauda epididymal sperm are almost immobile

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
male infertility due to globozoospermia DOID:0112312 J:168319




Genotype
MGI:5308362
cn22
Allelic
Composition
Tsc22d3tm1Ric/Y
Tg(Ddx4-cre)1Dcas/?
Genetic
Background
involves: C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ddx4-cre)1Dcas mutation (2 available)
Tsc22d3tm1Ric mutation (0 available); any Tsc22d3 mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype



Genotype
MGI:7294209
cn23
Allelic
Composition
Gt(ROSA)26Sortm2(CAG-Lancl1)Pfw/Gt(ROSA)26Sor+
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm2(CAG-Lancl1)Pfw mutation (0 available); any Gt(ROSA)26Sor mutation (993 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• males fed a high-fat diet (HFD) for 14 weeks (to induce obesity) show a significantly lower testicular expression of BAX and cleaved-caspase-3 protein than HFD-fed wild-type males
• males fed a HFD for 14 weeks show a significantly higher sperm forward motility (%) than HFD-fed wild-type males
• males fed a HFD for 14 weeks show a significantly higher sperm motility (%) than HFD-fed wild-type males
• males fed a HFD for 14 weeks show a significantly higher caudal epididymal sperm concentration than HFD-fed wild-type males
• males fed a HFD for 14 weeks show a less distorted arrangement of germ cells in the seminiferous tubules, a better Johnsen's score, and a significantly lower teratozoospermic ratio than HFD-fed wild-type males, indicating protection from HFD/obesity-induced spermatogenic defects

cellular
• males fed a HFD for 14 weeks show a significantly lower number of gammaH2AX+ germ cells per seminiferous tubule than HFD-fed wild-type males, indicating protection from HFD-induced oxidative damage
• males fed a high-fat diet (HFD) for 14 weeks (to induce obesity) show a significantly lower testicular expression of BAX and cleaved-caspase-3 protein than HFD-fed wild-type males
• males fed a HFD for 14 weeks show a significantly higher sperm forward motility (%) than HFD-fed wild-type males
• males fed a HFD for 14 weeks show a significantly higher sperm motility (%) than HFD-fed wild-type males
• males fed a HFD for 14 weeks show improved testicular redox imbalance with a significantly higher NADPH/NADP ratio and significantly lower malondialdehyde (MDA) and protein carbonyls in the testes than HFD-fed wild-type males, indicating protection from HFD-induced oxidative stress




Genotype
MGI:6451400
cn24
Allelic
Composition
Tg(Ddx4-cre)1Dcas/0
Rnf220em1Kust/Rnf220em1Kust
Genetic
Background
involves: C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rnf220em1Kust mutation (0 available); any Rnf220 mutation (323 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

embryo
• at E10.5, mice exhibit a ventral expansion of intermediate V0, dorsal expansion of ventral V3 neurons, and reduced V1, V2, and motor neurons between them compared with control mice

skeleton
• mice exhibit normal skeleton pattern and morphology

nervous system
• at E10.5, mice exhibit a ventral expansion of intermediate V0, dorsal expansion of ventral V3 neurons, and reduced V1, V2, and motor neurons between them compared with control mice
• in the dorsal neural tube at E10.5




Genotype
MGI:6681848
cn25
Allelic
Composition
Mettl3em1Chhe/Mettl3em1Chhe
Mettl14em1Chhe/Mettl14em1Chhe
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6J * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mettl14em1Chhe mutation (0 available); any Mettl14 mutation (36 available)
Mettl3em1Chhe mutation (0 available); any Mettl3 mutation (42 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or PLZF+ undifferentiated spermatogonia are detected at 4 weeks
• double knockout mice exhibit progressive loss of spermatogonial stem cells, similar to single Mettl3em1Chhe or Mettl14em1Chhe knockouts

cellular
• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or PLZF+ undifferentiated spermatogonia are detected at 4 weeks
• double knockout mice exhibit progressive loss of spermatogonial stem cells, similar to single Mettl3em1Chhe or Mettl14em1Chhe knockouts




Genotype
MGI:7311694
cn26
Allelic
Composition
Rad51tm1Csha/Rad51tm1Csha
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6J * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rad51tm1Csha mutation (0 available); any Rad51 mutation (31 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at P8, TEM showed complete loss of spermatogonia in seminiferous tubules
• at P12 and P60, Hematoxylin staining of seminiferous tubules showed complete germ cell loss
• at P10, no PLZF+ early spermatogonial stem cells (SSCs) are detected in seminiferous tubules
• however, GCNA+ male germ cells at still present at E18.5
• at P8, testes show severe depletion of germ cells in the seminiferous tubules; only SOX9+ Sertoli cells are detected at P8
• at P19 and P40, the number of SOX9+ Sertoli cells per tubule is significantly higher than in control testes
• at P40, testis size is significantly smaller than in control males
• from P10 to P40, testis weight is significantly lower than in control males
• however, testis weight is normal at P8
• at P12, seminiferous tubules display complete loss of spermatogonia and a Sertoli cell-only phenotype
• immunofluorescence staining of the Sertoli cell marker SOX9 showed that tubules only contain Sertoli cells at P8
• at P12, seminiferous tubules show complete loss of leptotene and zygotene spermatocytes
• immunofluorescence staining of meiotic markers showed no SYCP3+ or gammaH2AX+ cells in seminiferous tubules at P8
• adult male mice mated with wild-type fertile females for at least 6 months produce no pups

cellular
• at P12, seminiferous tubules show complete loss of leptotene and zygotene spermatocytes
• at P8, TEM showed complete loss of spermatogonia in seminiferous tubules
• at P12 and P60, Hematoxylin staining of seminiferous tubules showed complete germ cell loss
• at P10, no PLZF+ early spermatogonial stem cells (SSCs) are detected in seminiferous tubules
• however, GCNA+ male germ cells at still present at E18.5
• immunofluorescence staining of meiotic markers showed no SYCP3+ or gammaH2AX+ cells in seminiferous tubules at P8

endocrine/exocrine glands
• at P8, testes show severe depletion of germ cells in the seminiferous tubules; only SOX9+ Sertoli cells are detected at P8
• at P19 and P40, the number of SOX9+ Sertoli cells per tubule is significantly higher than in control testes
• at P40, testis size is significantly smaller than in control males
• from P10 to P40, testis weight is significantly lower than in control males
• however, testis weight is normal at P8




Genotype
MGI:6681844
cn27
Allelic
Composition
Mettl3em1Chhe/Mettl3em1Chhe
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6J * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mettl3em1Chhe mutation (0 available); any Mettl3 mutation (42 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• testes show defects in spermatogonial stem cell (SSC) development
• however, testes contain normal numbers of gonocytes at birth
• the number of undifferentiated spermatogonia (PLZF+ cells) is similar to that in controls up to P5 but significantly decreased by P7
• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or even PLZF+ undifferentiated spermatogonia are detected at 4 weeks
• however, Aaligned (Aal) spermatogonia (derived from As spermatogonia) remain, indicating that exhaustion of the SSC pool is possibly due to increased SSC proliferation
• little or no difference in apoptosis of PLZF+ spermatogonia is observed at P7
• mice exhibit progressive loss of SSCs, causing germ cell depletion
• at P10, EdU incorporation is significantly increased in GFRalpha1+ Asingle (As) spermatogonia (the most primitive set of spermatogonia), indicating higher proliferation of spermatogonial stem cells (SSCs)
• by 6 weeks of age, the seminiferous tubule epithelium is completely devoid of any germ cells, with only SOX9+ Sertoli cells remaining
• adult testes are smaller than normal
• males are sterile

cellular
• testes show defects in spermatogonial stem cell (SSC) development
• however, testes contain normal numbers of gonocytes at birth
• the number of undifferentiated spermatogonia (PLZF+ cells) is similar to that in controls up to P5 but significantly decreased by P7
• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or even PLZF+ undifferentiated spermatogonia are detected at 4 weeks
• however, Aaligned (Aal) spermatogonia (derived from As spermatogonia) remain, indicating that exhaustion of the SSC pool is possibly due to increased SSC proliferation
• little or no difference in apoptosis of PLZF+ spermatogonia is observed at P7
• mice exhibit progressive loss of SSCs, causing germ cell depletion
• N6-methyladenosine (m6A) levels are reduced by ~70% in THY1+ undifferentiated spermatogonia
• at P10, EdU incorporation is significantly increased in GFRalpha1+ Asingle (As) spermatogonia (the most primitive set of spermatogonia), indicating higher proliferation of spermatogonial stem cells (SSCs)
• mRNA m6A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation

homeostasis/metabolism
• mRNA m6A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation

endocrine/exocrine glands
• by 6 weeks of age, the seminiferous tubule epithelium is completely devoid of any germ cells, with only SOX9+ Sertoli cells remaining
• adult testes are smaller than normal




Genotype
MGI:6681845
cn28
Allelic
Composition
Mettl14em1Chhe/Mettl14em1Chhe
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6J * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mettl14em1Chhe mutation (0 available); any Mettl14 mutation (36 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or even PLZF+ undifferentiated spermatogonia are detected at 4 weeks
• mice exhibit progressive loss of spermatogonial stem cells (SSCs) causing germ cell depletion, similar to Mettl3em1Chhe/Mettl3em1Chhe Tg(Ddx4-cre)1Dcas/0 mice
• by 6 weeks of age, the seminiferous tubule epithelium is completely devoid of any germ cells, with only SOX9+ Sertoli cells remaining
• adult testes are smaller than normal

cellular
• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or even PLZF+ undifferentiated spermatogonia are detected at 4 weeks
• mice exhibit progressive loss of spermatogonial stem cells (SSCs) causing germ cell depletion, similar to Mettl3em1Chhe/Mettl3em1Chhe Tg(Ddx4-cre)1Dcas/0 mice
• N6-methyladenosine (m6A) levels are significantly reduced in THY1+ undifferentiated spermatogonia
• mRNA m6A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation

homeostasis/metabolism
• mRNA m6A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation

endocrine/exocrine glands
• by 6 weeks of age, the seminiferous tubule epithelium is completely devoid of any germ cells, with only SOX9+ Sertoli cells remaining
• adult testes are smaller than normal




Genotype
MGI:5795985
cn29
Allelic
Composition
Ppp2catm1.1Jmli/Ppp2catm1.2Jmli
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6J * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ppp2catm1.1Jmli mutation (0 available); any Ppp2ca mutation (25 available)
Ppp2catm1.2Jmli mutation (0 available); any Ppp2ca mutation (25 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at 4 weeks of age, seminiferous tubules exhibit vacuolation and disrupted arrangement of spermatogonia and primary spermatocytes
• by 8 weeks of age, fewer vacuole-like structures are found, germ cells appear disorganized, and elongated spermatozoa are absent
• at 4 weeks of age, seminiferous tubules exhibit vacuolation
• however, fewer vacuole-like structures are found by 8 weeks of age
• at 4 weeks of age, testes are significantly smaller than wild-type testes
• at 4 weeks of age, testes are ~20% the weight of control testes
• by 8 weeks of age, testes are ~50% the weight of control testes
• by 8 weeks of age, testes are almost completely devoid of mature spermatozoa, as shown by H&E staining of the seminiferous tubules and epididymides
• spermatogenesis is disrupted at all levels, as germ cells are either arranged in a disorderly manner or completely absent
• no normal sperm are observed in a sperm smear collected from P56 epididymides
• at P38, flow cytometric analysis revealed that meiosis is blocked at the diploid stage
• surprisingly, the numbers of haploid and diploid cells are almost identical at P56, indicating that some cells can proceed to the next stage; however, any haploid cells still present at P56 appear abnormal
• by 8 weeks of age, cauda epididymides contain some round cells of different sizes and shapes but no normal sperm
• males fail to produce pups

endocrine/exocrine glands
• at 4 weeks of age, seminiferous tubules exhibit vacuolation and disrupted arrangement of spermatogonia and primary spermatocytes
• by 8 weeks of age, fewer vacuole-like structures are found, germ cells appear disorganized, and elongated spermatozoa are absent
• at 4 weeks of age, seminiferous tubules exhibit vacuolation
• however, fewer vacuole-like structures are found by 8 weeks of age
• at 4 weeks of age, testes are significantly smaller than wild-type testes
• at 4 weeks of age, testes are ~20% the weight of control testes
• by 8 weeks of age, testes are ~50% the weight of control testes

cellular
• at P38, flow cytometric analysis revealed that meiosis is blocked at the diploid stage
• surprisingly, the numbers of haploid and diploid cells are almost identical at P56, indicating that some cells can proceed to the next stage; however, any haploid cells still present at P56 appear abnormal




Genotype
MGI:6838392
cn30
Allelic
Composition
Cenpvtm1c(EUCOMM)Hmgu/Cenpvtm1c(EUCOMM)Hmgu
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6N * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cenpvtm1c(EUCOMM)Hmgu mutation (0 available); any Cenpv mutation (60 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• as in other mice carrying the conditional allele activated in oocytes by Tg(Stra8-icre)1Reb or Tg(Spo11-cre)1Rsw

cellular
• as in other mice carrying the conditional allele activated in oocytes by Tg(Stra8-icre)1Reb or Tg(Spo11-cre)1Rsw




Genotype
MGI:7287664
cn31
Allelic
Composition
Ddx5tm1.1Arte/Ddx5tm1.1Arte
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: C57BL/6NTac * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ddx5tm1.1Arte mutation (2 available); any Ddx5 mutation (39 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at P6, TRA98+ spermatogonial stem cells (SSCs) are completely depleted in tubules
• at P0, numbers of TRA98+ germ cells (gonocytes) per unit area are reduced by 42%
• male germ cells are gradually lost from E18.5 to P6
• no sperm are released from the cauda epididymides in adult males
• single-cell transcriptome analysis showed that genes involved in cell cycle and glial cell line- derived neurotrophic factor (GDNF) pathway are significantly reduced in gonocytes
• at P2, testis sections show a significantly lower % of Gfra1+ gonocytes per unit area than control sections (2% versus 79%), indicating impaired gonocytes-to-spermatogonia transition
• at P2, testis sections show a significantly lower % of Ki67+ gonocytes per unit area than control sections (0.7% versus 41%), indicating impaired proliferation of gonocytes
• however, no increase in gonocyte apoptosis is detected by TUNEL staining at P0 or P2
• all seminiferous tubules are atrophic and empty in adult testes
• at P90, tubules are completely devoid of TRA98+ germ cells and contain only SOX9+ Sertoli cells
• at P6, TRA98+ SSCs are completely depleted in tubules, resulting in a Sertoli cell-only phenotype
• adult testes are significantly smaller than control testes
• adult testis to body weight ratio is significantly lower than that in control males
• adult males have no capacity to produce germ cells; no stage-specific subpopulations of spermatogenic cells are detected
• disruption of spermatogenesis occurs prior to spermatogonia formation
• no mature sperm are found in the cauda epididymides of adult males
• 3-mo-old male mice fail to produce offspring when mated with wild-type females
• however, copulatory plugs are observed

cellular
• at P6, TRA98+ spermatogonial stem cells (SSCs) are completely depleted in tubules
• at P0, numbers of TRA98+ germ cells (gonocytes) per unit area are reduced by 42%
• male germ cells are gradually lost from E18.5 to P6
• no sperm are released from the cauda epididymides in adult males
• single-cell transcriptome analysis showed that genes involved in cell cycle and glial cell line- derived neurotrophic factor (GDNF) pathway are significantly reduced in gonocytes
• at P2, testis sections show a significantly lower % of Gfra1+ gonocytes per unit area than control sections (2% versus 79%), indicating impaired gonocytes-to-spermatogonia transition
• at P2, testis sections show a significantly lower % of Ki67+ gonocytes per unit area than control sections (0.7% versus 41%), indicating impaired proliferation of gonocytes
• however, no increase in gonocyte apoptosis is detected by TUNEL staining at P0 or P2

endocrine/exocrine glands
• all seminiferous tubules are atrophic and empty in adult testes
• at P90, tubules are completely devoid of TRA98+ germ cells and contain only SOX9+ Sertoli cells
• at P6, TRA98+ SSCs are completely depleted in tubules, resulting in a Sertoli cell-only phenotype
• adult testes are significantly smaller than control testes
• adult testis to body weight ratio is significantly lower than that in control males




Genotype
MGI:6693629
cn32
Allelic
Composition
Foxj2tm1.1Mxc/Foxj2tm1.1Mxc
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxj2tm1.1Mxc mutation (0 available); any Foxj2 mutation (27 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• female mice exhibit normal fertility
• with unrepaired double strand breaks in spermatocytes
• arrested in pachytene

endocrine/exocrine glands

cellular
• with unrepaired double strand breaks in spermatocytes
• arrested in pachytene




Genotype
MGI:7285921
cn33
Allelic
Composition
Usp9xtm1Tuv/Y
Tg(Ddx4-cre)1Dcas/0
Genetic
Background
involves: FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ddx4-cre)1Dcas mutation (2 available)
Usp9xtm1Tuv mutation (0 available); any Usp9x mutation (24 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at 2 weeks of age or later, spermatogenic cells undergo apoptotic cell death at the early spermatocyte stage, as shown by TUNEL staining
• TUNEL+ spermatogenic cells are observed in the adluminal area nearest to the basal compartment throughout the postnatal to adult stages
• however, no differences in TUNEL+ cell number are observed in the newborn and 1-week-old stage
• at 12 weeks of age, ~85% of transverse sections of seminiferous tubules lack some spermatogenic cells
• ~3.3% of tubules contain both round and elongated spermatids but completely lack spermatocytes; ~68.8% of tubules contain a few spermatocytes and a few spermatids; and ~13.0% of tubules show almost complete lack of meiotic and post-meiotic spermatogenic cells in the adluminal compartment
• at 12 weeks of age, testes are grossly smaller than those in male controls
• at 12 weeks of age, testis weight x 100/body weight (%) is significantly lower than that in male controls
• testes show defective transition from the mitotic to meiotic phases and/or defective maintenance of early meiotic phase
• however, maintenance of undifferentiated GFRA1+/PLZF+ and differentiating KIT+ spermatogonia appear to be normal
• adult males contain only a few spermatozoa in the caudal epididymides
• some affected spermatids show aberrant condensed Hsc70t-positive signals as a residual body-like structure in the seminiferous tubules
• also, some elongated spermatids are degenerating and occasionally misaligned near the basement membrane, suggesting Sertoli cell phagocytosis of aberrant spermatids
• at 12 weeks of age, anti-SCP3 immunostaining showed that the relative number of spermatocytes is reduced to three-fourths of control testes
• however, spermatocytes that pass through meiotic differentiation and remain in affected seminiferous tubules show no defects in recombination and formation of the XY body
• PAS staining showed that some fully completed spermatozoa are abnormally retained in the seminiferous tubules containing the elongating spermatids at step 9-10, suggesting defects in spermiogenesis and/ or spermiation
• failure of spermiation subsequent to apoptotic cell death in early spermatocytes
• males are completely infertile
• however, vaginal plugs are observed in paired wild-type females

cellular
• adult males contain only a few spermatozoa in the caudal epididymides
• some affected spermatids show aberrant condensed Hsc70t-positive signals as a residual body-like structure in the seminiferous tubules
• also, some elongated spermatids are degenerating and occasionally misaligned near the basement membrane, suggesting Sertoli cell phagocytosis of aberrant spermatids
• at 12 weeks of age, anti-SCP3 immunostaining showed that the relative number of spermatocytes is reduced to three-fourths of control testes
• however, spermatocytes that pass through meiotic differentiation and remain in affected seminiferous tubules show no defects in recombination and formation of the XY body
• at 2 weeks of age or later, spermatogenic cells undergo apoptotic cell death at the early spermatocyte stage, as shown by TUNEL staining
• TUNEL+ spermatogenic cells are observed in the adluminal area nearest to the basal compartment throughout the postnatal to adult stages
• however, no differences in TUNEL+ cell number are observed in the newborn and 1-week-old stage

endocrine/exocrine glands
• at 12 weeks of age, ~85% of transverse sections of seminiferous tubules lack some spermatogenic cells
• ~3.3% of tubules contain both round and elongated spermatids but completely lack spermatocytes; ~68.8% of tubules contain a few spermatocytes and a few spermatids; and ~13.0% of tubules show almost complete lack of meiotic and post-meiotic spermatogenic cells in the adluminal compartment
• at 12 weeks of age, testes are grossly smaller than those in male controls
• at 12 weeks of age, testis weight x 100/body weight (%) is significantly lower than that in male controls





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory