All Phenotypes Ankrd31<em1Atot> MGI Mouse

• at 6-7 weeks of age, median oocyte numbers are 4.95-fold lower than in wild-type females

• reduction in oocyte number is associated with elevated rates of apoptosis

abnormal spermatocyte morphology ( J:276412 )

• both MEI4 and REC114 foci appear with delayed kinetics in spermatocytes; however, MEI4 and REC114 foci accumulate by zygotene and persist until SC formation is complete

• although MEI4 and REC114 foci eventually form, no MEI4 or REC114 aggregates are observed in PARs or autosome ends

abnormal meiosis ( J:276412 )

• accumulation of DSB recombination intermediates is delayed in meiocytes of both sexes

• persistence of recombination foci in late prophase spermatocytes and oocytes indicates defective and/or delayed DSB repair

absent chiasmata formation ( J:276412 )

• no spermatocytes exhibit chiasmata between X and Y chromosomes, as detected by FISH

• in addition, 10.12% of spermatocytes also lack a chiasma between an autosome pair

abnormal chromosomal synapsis ( J:276412 )

• at 16 dpc, fetuses exhibit higher rates of asynapsis in mid-pachytene oocytes (54.76%) than in wild-type oocytes (22.96%)

abnormal female meiosis ( J:276412 )

• oocytes show delayed accumulation of RAD51, DMC1, and RPA foci

abnormal male meiosis ( J:276412 )

• spermatocytes show delayed accumulation of RAD51, DMC1, and RPA foci; focus numbers remain abnormally low until early zygotene, increasing only after chromosome axes are fully formed (late zygotene-like stage)

• although MLH1 foci form on autosomes in normal numbers in most spermatocytes, MLH1 foci are always absent from the PARs of sex chromosomes in pachytene cells, indicating loss of PAR-associated crossovers

• RPA (DSB) foci are present only in 20.9% of spermatocytes in late zygotene or early pachytene

• a shift from the use of PRDM9-dependent B6 hotspots toward default hotspots is observed with a severe reduction in DSB activity noted in and around the PAR but with no significant changes in histone H3K4me3 distribution

abnormal X-Y chromosome synapsis during male meiosis ( J:276412 )

• PARs fail to synapse in 99.7% and 99% of pachytene spermatocytes from adult or juvenile male mice, respectively

• a dominant fraction of spermatocytes (76%) show unsynapsed X and Y chromosomes without any other obvious defects

• minor fractions show self-synapsed or short Y axes (12.5%), X-autosome fusions (6.6%), or circularized Y (4.8%)

arrest of male meiosis ( J:276412 )

• a fraction of spermatocytes progress to the first meiotic metaphase where they arrest

• metaphase arrest is likely due to loss of PAR-associated crossovers in spermatocytes

abnormal synaptonemal complex ( J:276412 )

• although chromosome axes do form with wild-type kinetics, spermatocytes of 13-day-old juvenile mice show delayed autosomal synaptonemal complex (SC) formation; despite this delay, most spermatocytes appear to complete autosomal SC formation in adults with no obvious non-homologous interactions in pachytene-stage spermatocytes

• SC formation is compromised in oocytes resulting in higher rates of asynapsis in mid-pachytene oocytes (54.76%) relative to wild-type oocytes (22.96%) in 16 dpc fetuses

• SC formation shows more penetrant defects between the pseudoautosomal regions (PARs) of the heterologous sex chromosomes in males

increased male germ cell apoptosis ( J:276412 )

• spermatocytes show elevated apoptosis after mid-pachytene stage

• most metaphase spermatocytes undergo apoptosis; only few post-meiotic cells are detected

abnormal female germ cell physiology ( J:276412 )

• ovaries of newborn females show an increased fraction of apoptotic oocytes, as determined by cleaved PARP1 staining

abnormal seminiferous tubule morphology ( J:276412 )

• a significantly increased proportion of seminiferous tubules contain metaphase I spermatocytes

• stage XII-like spermatocytes often contain chromosomes that do not line up at the metaphase plate, indicating chromosome alignment defects

decreased testis weight ( J:276412 )

• adult testes weight is 2.7-fold lower than in wild-type males

early reproductive senescence ( J:276412 )

• female mice lose their fertility faster than wild type females in advanced age

reduced female fertility ( J:276412 )

• after 28 weeks of age, females show a significant reduction in average numbers of pups per breeding week relative to age-matched wild-type females (0.45 versus 0.92, respectively)

• however, no significant differences are noted between 8-28 weeks of age

male infertility ( J:276412 )

• male mice fail to produce pups after 88 weeks of breeding