Mutations |
2 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Spruck CH, et al 2003 generated mice lacking Cks2, one of two mammalian homologs of the yeast Cdk1-binding proteins, Suc1 and Cks1, and found them to be viable but sterile in both sexes. Sterility is due to failure of both male and female germ cells to progress past the first meiotic metaphase. The chromosomal events up through the end of prophase I are normal in both CKS2-/- males and females, suggesting that the phenotype is due directly to failure to enter anaphase and not a consequence of a checkpoint-mediated metaphase I arrest.
Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: CKS1 Germ Line Exclusion is Essential for the Transition from Meiosis to Early Embryonic Development. Ellederova Z et al. (2019) CKS proteins bind cyclin-dependent kinases (CDKs) and play important roles in cell division control and development, though their precise molecular functions are not fully understood. Mammals express two closely related paralogs called CKS1 and CKS2, but only CKS2 is expressed in the germ line indicating it is solely responsible for regulating CDK functions in meiosis. Using cks2-/- knockout mice, we show that CKS2 is a crucial regulator of MPF (CDK1-Cyclin A/B) activity in meiosis. cks2-/- oocytes display reduced and delayed MPF activity during meiotic progression, leading to defects in germinal vesicle breakdown (GVBD), anaphase-promoting complex/cyclosome (APC/C) activation, and meiotic spindle assembly. cks2-/- germ cells express significantly reduced levels of MPF components CDK1 and Cyclins A1/B1. Additionally, injection of MPF + CKS2, but not MPF alone, restored normal GVBD in cks2-/- oocytes demonstrating GVBD is driven by a CKS2-dependent function of MPF. Moreover, we generated cks2cks1/cks1 knock-in mice and found CKS1 can compensate for CKS2 in meiosis in vivo, but homozygous embryos arrested development at the 2-5-cell stage. Collectively, our results show that CKS2 is a crucial regulator of MPF functions in meiosis and its paralog CKS1 must be excluded from the germ line for proper embryonic development.//////////////////
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