Ovca1, a candidate gene of the genetic modifier of Tp53, Mop2, affects mouse embryonic lethality
✍ Scribed by Min Liang; Bernard Ayanga; Shuhua Du; Andrew K. Godwin; Jennifer K. Hartsock; Susan C. Evans
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 476 KB
- Volume
- 47
- Category
- Article
- ISSN
- 1045-2257
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
In this study, we show genetic modifier genes of Tp53 that can exacerbate embryonic abnormalities. Using a mouse model in which CE/J mice were crossed with the Tp53‐null 129/Sv (129‐Trp53^tm1 Tyj^) mice, a subset of Tp53+/− and −/− male and female embryos died during gestation. Our hypothesis, based on the genotypes of survivors, is that two genetic modifiers and a Tp53 null allele lead to an increase in embryonic lethality. We previously identified a recessive modifier (Mop1) from CE/J mice on chromosome 11 centromeric to Tp53. We have uncovered a dominant modifier (Mop2) from 129/Sv mice telomeric to Tp53. We discovered a polymorphic change (321P→321S) of Ovca1 within the Mop2 locus of CE/J mice. This polymorphism increased both mRNA and protein levels of OVCA1 in various tissues. CE/J primary cells cultured from different tissues proliferated more rapidly than 129/Sv cells. In addition, CE/J cells cycled while 129/Sv cells had a higher arrest in the G1 phase. Transfection of Ovca1 containing the 321P polymorphism into CE/J cells caused a higher G1 arrest. The pattern of OVCA1 expression also changed from being diffuse throughout the cytoplasm in 129/Sv cells to being punctuate in the cytoplasm of CE/J cells. Tp53+/− abnormal embryos had more proliferating cells than normal embryos, but no obvious difference in differentiated neuronal cells. Tp53−/− small embryos had less differentiated neuronal cells and proliferating cells than normal embryos. Thus, a polymorphism of Ovca1, combined with Mop1, genetically modifies embryonic lethality in Tp53 deficient mice. © 2008 Wiley‐Liss, Inc.