Phenotypes associated with this allele

• Allele Symbol: Spidr^em1Jzc
• Allele Name: endonuclease-mediated mutation 1, Zi-Jiang Chen
• Allele ID: MGI:8283309
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spidr^em1Jzc/Spidr^em1Jzc	involves: C57BL/6 * DBA/2	MGI:8286390
cx2	Chek2^em4Gpt/Chek2^em4Gpt Spidr^em1Jzc/Spidr^em1Jzc	involves: C57BL/6 * C57BL/6JGpt * DBA/2	MGI:8286391

Genotype
MGI:8286390

hm1

• Allelic Composition: Spidr^em1Jzc/Spidr^em1Jzc
• Genetic Background: involves: C57BL/6 * DBA/2

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

reproductive system

increased male germ cell apoptosis ( J:335565 )

♂ • an increase in the number of apoptotic cells in testes

abnormal oogenesis ( J:335565 )

♀ • ovaries do not have follicles at various stages of oocyte development

decreased oocyte number ( J:335565 )

♀ • comparable numbers of oocytes are seen in ovaries at E13.5 when meiosis is initiated, and at E15.5, when oocytes are just entering the pachytene stage, but there are only 8.2% oocytes in ovaries at PD1

♀ • ovaries of 2-month-old females contain fewer oocytes and around 4 months, ovaries exhibit a near-complete loss of developing oocytes

abnormal female meiosis ( J:335565 )

♀ • oocytes exhibit defects in meiotic recombination

♀ • meiosis initiates normally and progresses to pachytene stage at E17.5, however only 7.5% of oocytes reach pachytene state at E17.5, indicating delayed meiotic progression in oocytes, although some oocytes are able to complete meiosis

♀ • oocytes exhibit a reduction in RAD51 and DMC1 foci at zygotene stage and the degree of RAD51 and DMC1 foci reduction is milder in oocytes compared to spermatocytes

♀ • oocytes exhibit a reduction of MLH1 foci at pachytene stage indicating that a small percentage of crossover-defective oocytes enter the mid-pachytene stage

♀ • most crossover-defective oocytes can escape spindle assembly checkpoint and can complete meiosis and develop backward into follicles to support fertility

♀ • univalent chromosomes caused by absence of chiasma are present in metaphase I oocytes

♀ • aneuploid eggs are present in metaphase II oocytes

abnormal ovary morphology ( J:335565 )

♀ • at 6 months of age, ovaries show complete loss of normal morphology and are fibrotic

abnormal ovarian follicle morphology ( J:335565 )

♀ • 3- and 5-week-old ovaries show reduced follicles and loss of follicles within 3 months

decreased primary ovarian follicle number ( J:335565 )

♀ • due to the depletion of primordial follicle pool, the primary follicles are decreased greatly at PD8 and PD15 and 3-5-week-old females exhibit fewer follicles, leading to premature ovarian insufficiency at 3-4 months

♀ • oocytes failing to proceed the pachytene stage is likely the reason for the exhaustion of primordial follicle pool

small ovary ( J:335565 )

♀ • 3- and 5-week-old ovaries show reduced size

ovary fibrosis ( J:335565 )

♀ • at 6 months of age, ovaries are fibrotic

small testis ( J:335565 )

♂ • 6-week-old males exhibit much smaller testes

decreased testis weight ( J:335565 )

♂ • adult testis weights are 3- to 4-fold lighter than that in wild-type males

premature ovarian failure ( J:335565 )

♀ • females exhibit premature ovarian insufficiency at 3-4 months

abnormal spermatogenesis ( J:335565 )

♂ • males exhibit impaired spermatogenesis in which no post-meiotic round or elongated spermatids are seen in the seminiferous tubules

azoospermia ( J:335565 )

♂ • no post-meiotic round or elongated spermatids are seen in the seminiferous tubules and no spermatozoa are seen in the cauda epididymis

abnormal male meiosis ( J:335565 )

♂ • crossover complexes and homologous recombination intermediates are defective in spermatocytes

♂ • a small proportion of spermatocytes enter the pachytene stage, however crossover formation is completely defective in these spermatocytes

♂ • spermatocytes exhibit a reduction in RAD51 foci and DMC1 foci at leptotene, zygotene, and pachytene stage, and an increase in RPA foci at these stages indicating accumulation of end-resected intermediates, however assembly of BLM foci during meiotic recombination is unaffected

abnormal X-Y chromosome synapsis during male meiosis ( J:335565 )

♂ • abnormal synapsis is seen in zygotene spermatocytes, with different regions of one chromosome synapsed with multiple partners, resulting in frequent synapsis between non-homologous chromosomes

♂ • 49.7% of zygotene cells show abnormal synapses of heterologous chromosomes

♂ • while double-strand break (DSB) formation is unaffected in spermatocytes, a considerable number of meiotic DSBs remain unpaired

arrest of male meiosis ( J:335565 )

♂ • mice lack spermatocytes beyond the pachytene stage and no diplotene spermatocytes are detectable in testes, indicating pachytene stage arrest

♂ • spermatocytes fail to proceed beyond the early-pachytene stage and only 4.8% of spermatocytes reach early-pachytene stage

reduced female fertility ( J:335565 )

♀ • females exhibit lower fertility and become completely sterile after a 3-month period

male infertility ( J:335565 )

♂

endocrine/exocrine glands

abnormal ovary morphology ( J:335565 )

♀ • at 6 months of age, ovaries show complete loss of normal morphology and are fibrotic

abnormal ovarian follicle morphology ( J:335565 )

♀ • 3- and 5-week-old ovaries show reduced follicles and loss of follicles within 3 months

decreased primary ovarian follicle number ( J:335565 )

♀ • due to the depletion of primordial follicle pool, the primary follicles are decreased greatly at PD8 and PD15 and 3-5-week-old females exhibit fewer follicles, leading to premature ovarian insufficiency at 3-4 months

♀ • oocytes failing to proceed the pachytene stage is likely the reason for the exhaustion of primordial follicle pool

small ovary ( J:335565 )

♀ • 3- and 5-week-old ovaries show reduced size

ovary fibrosis ( J:335565 )

♀ • at 6 months of age, ovaries are fibrotic

small testis ( J:335565 )

♂ • 6-week-old males exhibit much smaller testes

decreased testis weight ( J:335565 )

♂ • adult testis weights are 3- to 4-fold lighter than that in wild-type males

premature ovarian failure ( J:335565 )

♀ • females exhibit premature ovarian insufficiency at 3-4 months

cellular

azoospermia ( J:335565 )

♂ • no post-meiotic round or elongated spermatids are seen in the seminiferous tubules and no spermatozoa are seen in the cauda epididymis

abnormal male meiosis ( J:335565 )

♂ • crossover complexes and homologous recombination intermediates are defective in spermatocytes

♂ • a small proportion of spermatocytes enter the pachytene stage, however crossover formation is completely defective in these spermatocytes

♂ • spermatocytes exhibit a reduction in RAD51 foci and DMC1 foci at leptotene, zygotene, and pachytene stage, and an increase in RPA foci at these stages indicating accumulation of end-resected intermediates, however assembly of BLM foci during meiotic recombination is unaffected

abnormal X-Y chromosome synapsis during male meiosis ( J:335565 )

♂ • abnormal synapsis is seen in zygotene spermatocytes, with different regions of one chromosome synapsed with multiple partners, resulting in frequent synapsis between non-homologous chromosomes

♂ • 49.7% of zygotene cells show abnormal synapses of heterologous chromosomes

♂ • while double-strand break (DSB) formation is unaffected in spermatocytes, a considerable number of meiotic DSBs remain unpaired

arrest of male meiosis ( J:335565 )

♂ • mice lack spermatocytes beyond the pachytene stage and no diplotene spermatocytes are detectable in testes, indicating pachytene stage arrest

♂ • spermatocytes fail to proceed beyond the early-pachytene stage and only 4.8% of spermatocytes reach early-pachytene stage

increased male germ cell apoptosis ( J:335565 )

♂ • an increase in the number of apoptotic cells in testes

abnormal oogenesis ( J:335565 )

♀ • ovaries do not have follicles at various stages of oocyte development

decreased oocyte number ( J:335565 )

♀ • comparable numbers of oocytes are seen in ovaries at E13.5 when meiosis is initiated, and at E15.5, when oocytes are just entering the pachytene stage, but there are only 8.2% oocytes in ovaries at PD1

♀ • ovaries of 2-month-old females contain fewer oocytes and around 4 months, ovaries exhibit a near-complete loss of developing oocytes

abnormal female meiosis ( J:335565 )

♀ • oocytes exhibit defects in meiotic recombination

♀ • meiosis initiates normally and progresses to pachytene stage at E17.5, however only 7.5% of oocytes reach pachytene state at E17.5, indicating delayed meiotic progression in oocytes, although some oocytes are able to complete meiosis

♀ • oocytes exhibit a reduction in RAD51 and DMC1 foci at zygotene stage and the degree of RAD51 and DMC1 foci reduction is milder in oocytes compared to spermatocytes

♀ • oocytes exhibit a reduction of MLH1 foci at pachytene stage indicating that a small percentage of crossover-defective oocytes enter the mid-pachytene stage

♀ • most crossover-defective oocytes can escape spindle assembly checkpoint and can complete meiosis and develop backward into follicles to support fertility

♀ • univalent chromosomes caused by absence of chiasma are present in metaphase I oocytes

♀ • aneuploid eggs are present in metaphase II oocytes

mortality/aging

premature ovarian failure ( J:335565 )

♀ • females exhibit premature ovarian insufficiency at 3-4 months

Genotype
MGI:8286391

cx2

• Allelic Composition: Chek2^em4Gpt/Chek2^em4Gpt; Spidr^em1Jzc/Spidr^em1Jzc
• Genetic Background: involves: C57BL/6 * C57BL/6JGpt * DBA/2

reproductive system

azoospermia ( J:335565 )

♂ • no spermatozoa are seen in the epididymis

decreased spermatid number ( J:335565 )

♂ • males show rescue of spermatogenesis, with diplotene and metaphase I cells in testes and the presence of post-meiotic cells which can escape the checkpoint elimination and develop into round or elongating spermatids, but fewer post-meiotic cells are seen than in wild-type males

abnormal oogenesis ( J:335565 )

♀ • partial rescue of the oogenesis defects seen in single homozygous Spidr mutant females such that ovaries have follicles at various stages of oocyte development unlike single homozygous Spidr mutant females and oocyte loss is partially rescued such that females are able to produce more offspring than single homozygous Spidr mutants but still less than in wild-type females

decreased oocyte number ( J:335565 )

♀ • oocyte loss is partially rescued in adults, and females are able to produce more offspring than single homozygous Spidr mutant females within 6 months but still less than in wild-type females

reduced female fertility ( J:335565 )

♀ • females exhibit partial rescue of the subfertility seen in single homozygous Spidr mutants such that females are able to produce more offspring than single homozygous Spidr mutants but still lower fertility than in wild-type females

male infertility ( J:335565 )

♂ • males, but not females, are infertile

cellular

azoospermia ( J:335565 )

♂ • no spermatozoa are seen in the epididymis

decreased spermatid number ( J:335565 )

♂ • males show rescue of spermatogenesis, with diplotene and metaphase I cells in testes and the presence of post-meiotic cells which can escape the checkpoint elimination and develop into round or elongating spermatids, but fewer post-meiotic cells are seen than in wild-type males

abnormal oogenesis ( J:335565 )

♀ • partial rescue of the oogenesis defects seen in single homozygous Spidr mutant females such that ovaries have follicles at various stages of oocyte development unlike single homozygous Spidr mutant females and oocyte loss is partially rescued such that females are able to produce more offspring than single homozygous Spidr mutants but still less than in wild-type females

decreased oocyte number ( J:335565 )

♀ • oocyte loss is partially rescued in adults, and females are able to produce more offspring than single homozygous Spidr mutant females within 6 months but still less than in wild-type females