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Updated: May 20, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Mutations in Lyar and p53 are synergistically lethal in female mice

Guan Wang1, Christopher M Fulkerson, Reem Malek

  • 1Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, USA.

Birth Defects Research. Part A, Clinical and Molecular Teratology
|July 21, 2012
PubMed
Abstract

Insights

The study generated Lyar mutant mice to investigate its role in development. Loss of Lyar, especially with p53 deficiency, led to neural tube defects (NTDs) and embryonic lethality, identifying Lyar as a novel NTD candidate gene.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Ly-1 antibody reactive clone (LYAR) is a nucleolar protein linked to cell growth and embryonic stem cell self-renewal.
  • LYAR's precise role in development and its connection to medulloblastoma require further investigation.

Purpose of the Study:

  • To determine if LYAR is essential for mammalian cell growth and development.
  • To establish a mouse model for studying LYAR function and its interaction with p53.

Main Methods:

  • Generation of Lyar mutant mice using a gene-trap insertion.
  • Phenotypic analysis of Lyar mutant mice and mouse embryonic fibroblasts (MEFs).
  • Cross-breeding Lyar mutants with p53-deficient mice to assess compound mutant phenotypes.

Main Results:

  • Lyar mutant mice (homozygotes) were viable and fertile but exhibited impaired MEF growth.
  • Impaired MEF growth correlated with increased p53 and p21 levels, indicating a cellular stress response.
  • Compound Lyar/p53 mutant female embryos showed a high incidence of exencephaly, a neural tube defect (NTD).

Conclusions:

  • Lyar/p53 compound mutant mice provide a novel digenic model for studying NTDs.
  • LYAR is identified as a potential candidate gene involved in human NTDs.
  • Disruption of p53-mediated developmental checkpoints may elevate NTD risk in germline mutations.

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