Phenotypes associated with this allele

• Allele Symbol: Stra8^{em1(GFP/cre)Smoc}
• Allele Name: endonuclease-mediated mutation 1, Shanghai Model Organisms Center
• Allele ID: MGI:6356355
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mettl3^em1Chhe/Mettl3^em1Chhe Mettl14^em1Chhe/Mettl14^em1Chhe Stra8^em1(GFP/cre)Smoc/Stra8^+	involves: C57BL/6J	MGI:6681853
cn2	Mettl14^em1Chhe/Mettl14^em1Chhe Stra8^em1(GFP/cre)Smoc/Stra8^+	involves: C57BL/6J	MGI:6681852
cn3	Mettl3^em1Chhe/Mettl3^em1Chhe Stra8^em1(GFP/cre)Smoc/Stra8^+	involves: C57BL/6J	MGI:6681851
cn4	Firrm^em1Gpt/Firrm^em1Gpt Stra8^em1(GFP/cre)Smoc/Stra8^+	involves: C57BL/6JGpt	MGI:7641564

Genotype
MGI:6681853

cn1

• Allelic Composition: Mettl3^em1Chhe/Mettl3^em1Chhe; Mettl14^em1Chhe/Mettl14^em1Chhe; Stra8^{em1(GFP/cre)Smoc}/Stra8⁺
• Genetic Background: involves: C57BL/6J

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

reproductive system

oligozoospermia ( J:250428 )

♂ • caudal epididymal sperm count is only ~2% of that in control mice

teratozoospermia ( J:250428 )

♂

abnormal sperm head morphology ( J:250428 )

♂ • >80% of caudal epididymal sperm exhibit abnormal heads

♂ • elongated spermatids show abnormal head morphologies at epithelial stages I-VIII

abnormal spermatid morphology ( J:250428 )

♂ • elongated spermatids show abnormal head morphologies and their number is severely decreased from step 13 to step 16 at epithelial stages I-VIII

decreased sperm progressive motility ( J:250428 )

♂ • progressive motility of caudal epididymal sperm is severely reduced at 2 months of age

asthenozoospermia ( J:250428 )

♂ • CASA analysis revealed that total motility of caudal epididymal sperm is severely reduced at 2 months of age, indicating defects in sperm flagella

abnormal seminiferous tubule morphology ( J:250428 )

♂ • seminiferous tubules contain very few mature spermatozoa

♂ • however, no detectable abnormalities are observed in germ cells up to step 12 of elongating spermatids

small testis ( J:250428 )

♂ • adult testes are significantly smaller than those in controls

decreased testis weight ( J:250428 )

♂ • adult testis/body weight (%) is significantly lower than that in controls

arrest of spermiogenesis ( J:250428 )

♂ • spermatid differentiation is blocked in late stages of spermiogenesis

♂ • unexpectedly, male meiosis is normal

cellular

oligozoospermia ( J:250428 )

♂ • caudal epididymal sperm count is only ~2% of that in control mice

teratozoospermia ( J:250428 )

♂

abnormal sperm head morphology ( J:250428 )

♂ • >80% of caudal epididymal sperm exhibit abnormal heads

♂ • elongated spermatids show abnormal head morphologies at epithelial stages I-VIII

abnormal spermatid morphology ( J:250428 )

♂ • elongated spermatids show abnormal head morphologies and their number is severely decreased from step 13 to step 16 at epithelial stages I-VIII

decreased sperm progressive motility ( J:250428 )

♂ • progressive motility of caudal epididymal sperm is severely reduced at 2 months of age

asthenozoospermia ( J:250428 )

♂ • CASA analysis revealed that total motility of caudal epididymal sperm is severely reduced at 2 months of age, indicating defects in sperm flagella

abnormal epigenetic regulation of gene expression ( J:250428 )

♂ • N⁶-methyladenosine (m⁶A) levels in spermatids of double knockout mice are significantly lower than those in single Mettl3^em1Chhe or Mettl14^em1Chhe knockouts

♂ • however, no significant differences in m⁶A levels are noted between double knockout and single knockout spermatocytes

abnormal translation ( J:250428 )

♂ • spermatids from double mutant mice show impaired translation of haploid-specific genes that are essential for spermiogenesis

homeostasis/metabolism

abnormal translation ( J:250428 )

♂ • spermatids from double mutant mice show impaired translation of haploid-specific genes that are essential for spermiogenesis

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:250428 )

♂ • seminiferous tubules contain very few mature spermatozoa

♂ • however, no detectable abnormalities are observed in germ cells up to step 12 of elongating spermatids

small testis ( J:250428 )

♂ • adult testes are significantly smaller than those in controls

decreased testis weight ( J:250428 )

♂ • adult testis/body weight (%) is significantly lower than that in controls

Genotype
MGI:6681852

cn2

• Allelic Composition: Mettl14^em1Chhe/Mettl14^em1Chhe; Stra8^{em1(GFP/cre)Smoc}/Stra8⁺
• Genetic Background: involves: C57BL/6J

reproductive system

reproductive system phenotype ( J:250428 )

♂N • male mice are fertile and exhibit normal spermatogenesis with no detectable defects in meiosis or spermiogenesis

cellular

abnormal epigenetic regulation of gene expression ( J:250428 )

♂ • N⁶-methyladenosine (m⁶A) levels are reduced by 55-65% in pachytene spermatocytes and by 45% in round spermatids relative to controls

Genotype
MGI:6681851

cn3

• Allelic Composition: Mettl3^em1Chhe/Mettl3^em1Chhe; Stra8^{em1(GFP/cre)Smoc}/Stra8⁺
• Genetic Background: involves: C57BL/6J

reproductive system

reproductive system phenotype ( J:250428 )

♂N • male mice are fertile and exhibit normal spermatogenesis with no detectable defects in meiosis or spermiogenesis

cellular

abnormal epigenetic regulation of gene expression ( J:250428 )

♂ • N⁶-methyladenosine (m⁶A) levels are reduced by 55-65% in pachytene spermatocytes and by 45% in round spermatids relative to controls

Genotype
MGI:7641564

cn4

• Allelic Composition: Firrm^em1Gpt/Firrm^em1Gpt; Stra8^{em1(GFP/cre)Smoc}/Stra8⁺
• Genetic Background: involves: C57BL/6JGpt

reproductive system

decreased oocyte number ( J:344887 )

♀ • fewer oocytes are detected at P1 and P3

absent oocytes ( J:344887 )

♀ • no oocytes are observed at P10, suggesting premature ovarian failure

decreased male germ cell number ( J:344887 )

♂ • no round or elongated spermatids are observed in the seminiferous tubules at P42

♂ • ratios of WT1+ Sertoli cells to PLZF+ cells (undifferentiated and differentiating spermatogonia) are similar to those in wild-type testes

azoospermia ( J:344887 )

♂ • at P42, epididymides are consistently devoid of mature spermatozoa

abnormal chromosomal synapsis ( J:344887 )

♂ • incomplete synapsis is observed in testes sections stained for SYCP1 and SYCP3 and in spermatocytes stained for HORMAD1 (an unsynapsed chromosome marker) and SYCP3

abnormal female meiosis ( J:344887 )

♀ • at P1, meiotic primordial germ cells (PGCs) show defects in RAD51 and DMC1 removal; PGCs are RAD51- and DMC1-positive throughout the nucleus, whereas wild-type PGCs are at diplotene stage with no or weak RAD51/DMC1 signals

abnormal male meiosis ( J:344887 )

♂ • persistent foci of RAD51 and DMC1 foci (markers of early recombination intermediates in meiosis) are found in spermatocytes at the zygotene-like stage; extensive RAD51 and DMC1 foci are detected on both unsynapsed and synapsed regions

♂ • number of RAD51 foci only shows a 13% decrease while number of DMC1 foci exhibits just a 23% decrease during the early-zygotene to zygotene-like transition, indicating defects in RAD51/DMC1 removal during meiotic recombination

♂ • at P42, intensity of RAD51 and DMC1 signals is stronger than in wild-type testes

♂ • RAD51 and DMC1 foci frequently co-localize with TEX11 and SHOC1; in zygotene-like spermatocytes, co-localization frequencies for RAD51/TEX11 and DMC1/SHOC1 pairs are 42% and 37%, respectively

♂ • fewer MSH4 foci are observed in zygotene-like spermatocytes; 87% of MSH4 foci co-localize with DMC1, while MLH1 foci (a marker of late recombination intermediates) are almost absent, suggesting that defective RAD51/DMC1 removal impairs meiotic homologous recombination

abnormal synaptonemal complex ( J:344887 )

♂ • even in the most advanced zygonema-like spermatocytes, SYCP1 stretches do not extend to the full length, remaining short and sometimes increasing in numbers

increased male germ cell apoptosis ( J:344887 )

♂ • at P42, testes show a massive number of TUNEL+ cells

small ovary ( J:344887 )

♀ • ovaries are significantly smaller than in wild-type controls

ovary degeneration ( J:344887 )

♀ • after P25, ovaries are almost undetectable and hard to be dissected from the oviducts

abnormal seminiferous tubule morphology ( J:344887 )

♂ • at P42, seminiferous tubules are smaller with large cavities and no round or elongated spermatids are observed

small seminiferous tubules ( J:344887 )

♂

small testis ( J:344887 )

♂ • at P42, testes are significantly smaller than in wild-type controls

decreased testis weight ( J:344887 )

♂ • at P42, testis weight is 21.05 +/- 0.80 mg versus 72.48 +/- 3.01 mg in wild-type controls

premature ovarian failure ( J:344887 )

♀

arrest of spermatogenesis ( J:344887 )

♂ • spermatogenesis is arrested at meiotic prophase I

arrest of male meiosis ( J:344887 )

♂ • spermatocytes show impaired meiotic prophase I progression; at P21, pachynema and diplonema with gammaH2AX signals (marking double strand breaks) on sex bodies are not found, unlike in wild-type testes

♂ • ~60% of spermatocytes are arrested at a zygotene-like stage that is similar to the late-zygonema in wild-type testes

infertility ( J:344887 )

• both male and female mice are infertile

female infertility ( J:344887 )

♀

male infertility ( J:344887 )

♂

cellular

decreased oocyte number ( J:344887 )

♀ • fewer oocytes are detected at P1 and P3

absent oocytes ( J:344887 )

♀ • no oocytes are observed at P10, suggesting premature ovarian failure

decreased male germ cell number ( J:344887 )

♂ • ratios of WT1+ Sertoli cells to PLZF+ cells (undifferentiated and differentiating spermatogonia) are similar to those in wild-type testes

♂ • no round or elongated spermatids are observed in the seminiferous tubules at P42

azoospermia ( J:344887 )

♂ • at P42, epididymides are consistently devoid of mature spermatozoa

abnormal chromosomal synapsis ( J:344887 )

♂ • incomplete synapsis is observed in testes sections stained for SYCP1 and SYCP3 and in spermatocytes stained for HORMAD1 (an unsynapsed chromosome marker) and SYCP3

abnormal female meiosis ( J:344887 )

♀ • at P1, meiotic primordial germ cells (PGCs) show defects in RAD51 and DMC1 removal; PGCs are RAD51- and DMC1-positive throughout the nucleus, whereas wild-type PGCs are at diplotene stage with no or weak RAD51/DMC1 signals

abnormal male meiosis ( J:344887 )

♂ • persistent foci of RAD51 and DMC1 foci (markers of early recombination intermediates in meiosis) are found in spermatocytes at the zygotene-like stage; extensive RAD51 and DMC1 foci are detected on both unsynapsed and synapsed regions

♂ • number of RAD51 foci only shows a 13% decrease while number of DMC1 foci exhibits just a 23% decrease during the early-zygotene to zygotene-like transition, indicating defects in RAD51/DMC1 removal during meiotic recombination

♂ • at P42, intensity of RAD51 and DMC1 signals is stronger than in wild-type testes

♂ • RAD51 and DMC1 foci frequently co-localize with TEX11 and SHOC1; in zygotene-like spermatocytes, co-localization frequencies for RAD51/TEX11 and DMC1/SHOC1 pairs are 42% and 37%, respectively

♂ • fewer MSH4 foci are observed in zygotene-like spermatocytes; 87% of MSH4 foci co-localize with DMC1, while MLH1 foci (a marker of late recombination intermediates) are almost absent, suggesting that defective RAD51/DMC1 removal impairs meiotic homologous recombination

arrest of male meiosis ( J:344887 )

♂ • spermatocytes show impaired meiotic prophase I progression; at P21, pachynema and diplonema with gammaH2AX signals (marking double strand breaks) on sex bodies are not found, unlike in wild-type testes

♂ • ~60% of spermatocytes are arrested at a zygotene-like stage that is similar to the late-zygonema in wild-type testes

abnormal synaptonemal complex ( J:344887 )

♂ • even in the most advanced zygonema-like spermatocytes, SYCP1 stretches do not extend to the full length, remaining short and sometimes increasing in numbers

increased male germ cell apoptosis ( J:344887 )

♂ • at P42, testes show a massive number of TUNEL+ cells

endocrine/exocrine glands

small ovary ( J:344887 )

♀ • ovaries are significantly smaller than in wild-type controls

ovary degeneration ( J:344887 )

♀ • after P25, ovaries are almost undetectable and hard to be dissected from the oviducts

abnormal seminiferous tubule morphology ( J:344887 )

♂ • at P42, seminiferous tubules are smaller with large cavities and no round or elongated spermatids are observed

small seminiferous tubules ( J:344887 )

♂

small testis ( J:344887 )

♂ • at P42, testes are significantly smaller than in wild-type controls

decreased testis weight ( J:344887 )

♂ • at P42, testis weight is 21.05 +/- 0.80 mg versus 72.48 +/- 3.01 mg in wild-type controls

premature ovarian failure ( J:344887 )

♀

mortality/aging

premature ovarian failure ( J:344887 )

♀