Phenotypes Associated with This Genotype

Genotype
MGI:5775157

• Allelic Composition: Kif18a^gcd2/Kif18a^gcd2
• Genetic Background: CAST.129S1(B6)-Kif18a^gcd2/JcsMmjax

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

cellular

abnormal spermatogonia morphology ( J:222418 )

• mitotically dividing spermatogonial cells (MVH+) from pre-pubertal mutant testes show poor spindle organization and impaired mitotic chromosome alignment

decreased germ cell number ( J:222418 )

• mutant fetal gonads exhibit cell cycle arrest and apoptosis, ultimately leading to germ cell depletion

abnormal cell physiology ( J:222418 )

• primary MEFs derived from mutant E12.5-E13.5 embryos show reduced viability by trypan blue exclusion relative to wild-type MEFs

abnormal cell cycle checkpoint function ( J:222418 )

• cell cycle analysis on E12.5 fetal gonads showed a significantly higher % of mutant germ (MVH+) cells in G2/M and a corresponding reduction in the % of germ cells in G1 relative to wild-type controls

• phosphorylated histone H3 and TUNEL labeling, both indicative of G2/M checkpoint activation, are significantly increased in mutant germ cells

• however, no significant differences in cell cycle distribution or histone H3 phosphorylation are detected in gonadal somatic (MVH-) cells

abnormal mitosis ( J:222418 )

• mutant MEFs show a 7-fold increase in the ratio of preanaphase mitotic cells with unaligned chromosomes; chromosomes are not aligned in live MEFs prior to anaphase

• mutant germ cells in the E12.5 fetal gonad exhibit similar chromosome alignment defects and undergo mitotic arrest

• however, mutant MEFs show no evidence of mitotic (G2 to M) arrest; progression from nuclear envelope breakdown to anaphase is comparable to wild-type

abnormal mitotic spindle assembly checkpoint ( J:222418 )

• germ cell specific mitotic arrest due to kinetochore-microtubule attachment defects, as shown by persistent MAD2 localization to mutant kinetochores at metaphase in spermatogonia from pre-pubertal testes

abnormal mitotic spindle morphology ( J:222418 )

• mitotically dividing spermatogonial cells (MVH+) from pre-pubertal mutant testes show poor spindle organization and impaired mitotic chromosome alignment

increased apoptosis ( J:222418 )

• a significantly higher % of mutant fetal germ cells are TUNEL+, indicating increased apoptosis

• in contrast, mutant MEFs show no evidence of increased apoptosis

decreased fibroblast proliferation ( J:222418 )

• primary MEFs derived from mutant E12.5-E13.5 embryos grow slowly in culture relative to wild-type or heterozygous control MEFs

reproductive system

abnormal spermatogonia morphology ( J:222418 )

• mitotically dividing spermatogonial cells (MVH+) from pre-pubertal mutant testes show poor spindle organization and impaired mitotic chromosome alignment

decreased germ cell number ( J:222418 )

• mutant fetal gonads exhibit cell cycle arrest and apoptosis, ultimately leading to germ cell depletion

infertility ( J:222418 )

• both male and female mutant mice are infertile