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The Hira gene encodes a nuclear WD40 domain protein homologous to the yeast transcriptional corepressors Hir1p and Hir2p. Using targeted mutagenesis we demonstrate that Hira is essential for murine embryogenesis. Analysis of inbred 129Sv embryos carrying the null mutation revealed an initial requirement during gastrulation, with many mutant embryos having a distorted primitive streak. Mutant embryos recovered at later stages have a range of malformations with axial and paraxial mesendoderm being particularly affected, a finding consistent with the disruption of gastrulation seen earlier in development. This phenotype could be partially rescued by a CD1 genetic background, although the homozygous mutation was always lethal by embryonic day 11, with death probably resulting from abnormal placentation and failure of cardiac morphogenesis.

Type

Journal article

Journal

Mol Cell Biol

Publication Date

04/2002

Volume

22

Pages

2318 - 2328

Keywords

Animals, Blotting, Western, Body Patterning, Cell Cycle Proteins, Congenital Abnormalities, Embryo Loss, Embryonic and Fetal Development, Gastrula, Gene Deletion, Genes, Essential, Histone Chaperones, Homozygote, Immunohistochemistry, In Situ Hybridization, Mesoderm, Mice, Mutagenesis, Site-Directed, Nervous System, Nuclear Proteins, Phenotype, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors