| First Author | Wang G | Year | 2012 |
| Journal | Birth Defects Res A Clin Mol Teratol | Volume | 94 |
| Issue | 9 | Pages | 729-37 |
| PubMed ID | 22815056 | Mgi Jnum | J:263530 |
| Mgi Id | MGI:6188741 | Doi | 10.1002/bdra.23048 |
| Citation | Wang G, et al. (2012) Mutations in Lyar and p53 are synergistically lethal in female mice. Birth Defects Res A Clin Mol Teratol 94(9):729-37 |
| abstractText | BACKGROUND: Ly-1 antibody reactive clone (LYAR) is a nucleolar zinc finger protein that has been implicated in cell growth, self-renewal of embryonic stem cells, and medulloblastoma. To test whether LYAR is critical for cell growth and development, we generated Lyar mutant mice. METHODS: Mice carrying the mutant Lyar(gt) allele were generated from embryonic stem cells that contained a gene-trap insertion in the Lyar gene. Phenotypic analyses were performed on Lyar mutant mice and mouse embryonic fibroblasts. Lyar(gt/gt) mice were crossed to mice lacking the p53 tumor suppressor protein and Lyar/p53 compound mutants scored for external abnormalities. RESULTS: Lyar(gt/gt) homozygotes are viable, fertile, and indistinguishable from wild type littermates. However, the growth of Lyar(+/gt) and Lyar(gt/gt) mouse embryonic fibroblasts (MEFs) was impaired, coincident with an increase in the steady-state level of p53 and a key p53 effector of growth arrest, p21, suggesting that a cellular stress response is triggered in the absence of a wild type level of LYAR. Remarkably, the majority of Lyar(+/gt) and Lyar(gt/gt) female mice lacking p53 mice failed to survive. The neural tube defect (NTD) exencephaly was observed in approximately 26% and approximately 61% of female Lyar(+/gt;) p53(-/-) and Lyar(gt/gt;) p53(-/-) embryos, respectively. CONCLUSIONS: Lyar/p53 mutant mice represent a new digenic model of NTDs. Furthermore, these studies identify Lyar as a novel candidate gene for a role in human NTDs. These results provide new data to support the idea that loss of a p53-mediated developmental checkpoint may increase the risk of NTDs owing to some germline mutations. |
