Phenotypes associated with this allele

• Allele Symbol: Morc2a^{tm1c(KOMP)Wtsi}
• Allele Name: targeted mutation 1c, Wellcome Trust Sanger Institute
• Allele ID: MGI:8296675
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Morc2a^tm1c(KOMP)Wtsi/Morc2a^tm1d(KOMP)Wtsi Stra8^em1(GFP/cre)Smoc/Stra8^+	involves: 129S4/SvJaeSor * C57BL/6N	MGI:8297289
cn2	Morc2a^tm1c(KOMP)Wtsi/Morc2a^tm1d(KOMP)Wtsi Tg(Ddx4-cre)1Dcas/0	involves: 129S4/SvJaeSor * C57BL/6N * FVB	MGI:8297287

Genotype
MGI:8297289

cn1

• Allelic Composition: Morc2a^{tm1c(KOMP)Wtsi}/Morc2a^{tm1d(KOMP)Wtsi}; Stra8^{em1(GFP/cre)Smoc}/Stra8⁺
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6N

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

reproductive system

reproductive system phenotype ( J:377141 )

♀N • adult female mice exhibit normal fertility with no significant differences in ovarian histology or litter size relative to control females

decreased male germ cell number ( J:377141 )

♂ • testes from 24-day-old mice show a marked loss of spermatocytes; early pachytene cells are present but mid to late pachytene and diplotene cells are severely depleted

azoospermia ( J:377141 )

♂ • epididymis of 3-month-old males lacks sperm

abnormal male meiosis ( J:377141 )

♂ • males show a partial meiotic block at the early to mid pachytene transition

♂ • 70% of mid pachytene spermatocytes from 24-day-old testes still have gamma-H2AX (a marker of DNA damage response) localized to autosomes as flares, suggesting a defect in meiotic double strand break repair in pachytene cells

♂ • however, chromosomal synapsis appears normal in pachytene spermatocyte

small testis ( J:377141 )

♂ • 3-month-old males have significantly smaller testes than control males

decreased testis weight ( J:377141 )

♂ • 3-month-old males show a significant reduction in testis/body weight ratio

arrest of spermiogenesis ( J:377141 )

♂ • males show a complete post-meiotic spermiogenic arrest at step 4 of round spermatids

abnormal epididymis morphology ( J:377141 )

♂ • epididymis of 3-month-old males contains sloughed round spermatids instead of sperm

male infertility ( J:377141 )

♂ • males are sterile

cellular

decreased male germ cell number ( J:377141 )

♂ • testes from 24-day-old mice show a marked loss of spermatocytes; early pachytene cells are present but mid to late pachytene and diplotene cells are severely depleted

azoospermia ( J:377141 )

♂ • epididymis of 3-month-old males lacks sperm

abnormal male meiosis ( J:377141 )

♂ • males show a partial meiotic block at the early to mid pachytene transition

♂ • 70% of mid pachytene spermatocytes from 24-day-old testes still have gamma-H2AX (a marker of DNA damage response) localized to autosomes as flares, suggesting a defect in meiotic double strand break repair in pachytene cells

♂ • however, chromosomal synapsis appears normal in pachytene spermatocyte

abnormal epigenetic regulation of gene expression ( J:377141 )

♂ • pachytene spermatocytes show a significant reduction of histone H3 lysine 9 trimethylation (H3K9me3) on sex chromosomes (and to a lesser extent, autosomes) resulting in increased expression of sex chromosome-linked genes, with preferential upregulation of X-linked genes

♂ • failure in meiotic sex chromosome inactivation (MSCI) leads to post-meiotic arrest

♂ • however, adult testes exhibit no de-repression of long interspersed nuclear element 1 (LINE1) and intra-cisternal A-type particle (IAP) retrotransposons by immunofluorescence of LINE1 ORF1 and IAP GAG; RNA-seq analysis indicates no upregulation of evolutionarily young LINE1 retrotransposons (L1Md_A, L1_Md_T, and L1_Md_Gf) or IAPEz-int in pachytene spermatocytes

endocrine/exocrine glands

small testis ( J:377141 )

♂ • 3-month-old males have significantly smaller testes than control males

decreased testis weight ( J:377141 )

♂ • 3-month-old males show a significant reduction in testis/body weight ratio

Genotype
MGI:8297287

cn2

• Allelic Composition: Morc2a^{tm1c(KOMP)Wtsi}/Morc2a^{tm1d(KOMP)Wtsi}; Tg(Ddx4-cre)1Dcas/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6N * FVB

reproductive system

reproductive system phenotype ( J:377141 )

♀N • adult female mice exhibit normal fertility with no significant differences in ovarian histology or litter size relative to control females

azoospermia ( J:377141 )

♂ • epididymis of 8-week-old males lacks sperm

abnormal chromosomal synapsis ( J:377141 )

♂ • immunofluorescence of spread nuclei of spermatocytes from P18 testes using antibodies against SYCP1 (synaptonemal complex protein 1; a major structural component of the transverse filaments of the synaptonemal complex) and SYCP3 (synaptonemal complex protein 3; a crucial structural component of chromosomal axial elements) shows that axial elements are assembled but fail to form synapsis, as evidenced by the absence of SYCP1

arrest of male meiosis ( J:377141 )

♂ • histological analysis of testes from 8-week-old males indicates meiotic arrest in all seminiferous tubules at the zygotene-like stage

abnormal synaptonemal complex ( J:377141 )

♂ • chromosomal axial elements (SYCP3) are assembled but fail to form synapsis, as evidenced by the absence of SYCP1 (transverse filaments)

♂ • SYCP3 forms large polycomplexes (condensates) in leptotene and zygotene spermatocytes

increased testis apoptosis ( J:377141 )

♂ • TUNEL analysis of 8-week-old testes shows a significant increase in the number of TUNEL+ cells per seminiferous tubule

abnormal DNA methylation during gametogenesis ( J:377141 )

♂ • at P10, the level of CpG methylation in L1MdA_I (a young LINE1 element) is only 41% versus 92% in control testes, as assessed by bisulfite sequencing; similarly, the level of CpG methylation in IAP is only 43% versus 85% in control testis

♂ • RNA-seq analysis shows that several evolutionarily young transposable element (TE) subfamilies are upregulated in P10 testes, suggesting that DNA hypomethylation might be the cause of retrotransposon de-repression in pre-meiotic male germ cells

small testis ( J:377141 )

♂ • 8-week-old males have significantly smaller testes than control males

decreased testis weight ( J:377141 )

♂ • 8-week-old males show a significant reduction in testis/body weight ratio

abnormal epididymis morphology ( J:377141 )

♂ • epididymis of 8-week-old males lacks sperm and contains only cellular debris

male infertility ( J:377141 )

♂ • males are sterile

cellular

azoospermia ( J:377141 )

♂ • epididymis of 8-week-old males lacks sperm

abnormal chromosomal synapsis ( J:377141 )

♂ • immunofluorescence of spread nuclei of spermatocytes from P18 testes using antibodies against SYCP1 (synaptonemal complex protein 1; a major structural component of the transverse filaments of the synaptonemal complex) and SYCP3 (synaptonemal complex protein 3; a crucial structural component of chromosomal axial elements) shows that axial elements are assembled but fail to form synapsis, as evidenced by the absence of SYCP1

arrest of male meiosis ( J:377141 )

♂ • histological analysis of testes from 8-week-old males indicates meiotic arrest in all seminiferous tubules at the zygotene-like stage

abnormal synaptonemal complex ( J:377141 )

♂ • chromosomal axial elements (SYCP3) are assembled but fail to form synapsis, as evidenced by the absence of SYCP1 (transverse filaments)

♂ • SYCP3 forms large polycomplexes (condensates) in leptotene and zygotene spermatocytes

increased testis apoptosis ( J:377141 )

♂ • TUNEL analysis of 8-week-old testes shows a significant increase in the number of TUNEL+ cells per seminiferous tubule

abnormal epigenetic regulation of gene expression ( J:377141 )

♂ • pre-meiotic male germ cells show a failure in silencing of young long interspersed nuclear element 1 (LINE1) and intra-cisternal A-type particle (IAP) retrotransposons

♂ • immunofluorescent analysis shows that LINE1 is sharply upregulated in spermatocytes but not in spermatogonia, whereas IAP is upregulated in both spermatogonia and spermatocytes from P18 testes; both LINE1 and IAP are upregulated in gonocytes from newborn (P0) testes

♂ • qRT-PCR analysis shows that both LINE1 and IAP are upregulated in P10, P14, and P60 testes, with LINE1 ORF1 protein abundance sharply increased at P10 and P14

♂ • however, PIWIL4/MIWI2 is still localized to the nucleus of gonocytes in P0 testes, suggesting that activation of retrotransposons occurs independently or downstream of the piRNA pathway

abnormal DNA methylation during gametogenesis ( J:377141 )

♂ • at P10, the level of CpG methylation in L1MdA_I (a young LINE1 element) is only 41% versus 92% in control testes, as assessed by bisulfite sequencing; similarly, the level of CpG methylation in IAP is only 43% versus 85% in control testis

♂ • RNA-seq analysis shows that several evolutionarily young transposable element (TE) subfamilies are upregulated in P10 testes, suggesting that DNA hypomethylation might be the cause of retrotransposon de-repression in pre-meiotic male germ cells

endocrine/exocrine glands

increased testis apoptosis ( J:377141 )

♂ • TUNEL analysis of 8-week-old testes shows a significant increase in the number of TUNEL+ cells per seminiferous tubule

small testis ( J:377141 )

♂ • 8-week-old males have significantly smaller testes than control males

decreased testis weight ( J:377141 )

♂ • 8-week-old males show a significant reduction in testis/body weight ratio