International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

Table of Contents * Genes, Physical Mapping and Sequencing * Gene Identification * Bioinformatics * Common Resources * RIKEN Session * Functional Genomics * Complex Traits * Mutagenesis * Developmental Genetics and Differentiation * Verne Chapman Memorial Lecture I and II

I28. Inadequate Differentiation of Mesoderm Derived Cells in Mouse Odz4 Mutant Embryos

H. Nakamura, S. E. Thomas, and M. J. Justice
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza Houston, Texas, 77030, USA

Through ethylnitrosourea (ENU) mutagenesis, numerous mutant alleles (reflecting complete loss, partial loss, or gain of function) for any gene of interest can be generated, thus revealing the function(s) of that gene. Saturation mutagenesis with ENU using a large deletion at albino locus on mouse Chromosome 7 revealed many new functional units including a number of embryonic lethal mutations (Rinchik et. al., 1990, 1999). Our focus is on one of these loci, called l7Rn3. Five of the six ENU-induced alleles of l7Rn3 die during embryogenesis, whereas one in viable. We recently found that these embryonic lethal mutant alleles showed a wide range of phenotypes. Embryos homozygous for l7Rn3 m1 (believed to be a loss of function allele) die around E8.0, whereas l7Rn3 m4 embryos (believed to be a hypomorphic alleles) die at E9.5. At E6.5, all homozygous embryos are morphologically normal, but the phenotype is obvious at E8.0 when wild type embryos have started to undergo extensive neural and axial development. Mutant embryos exhibited gastrulation defect and l7Rn3 m4 have a deficiency in axial mesoderm.

To explore the nature of the mesoderm defect in the mutant, we have undertaken additional phenotype analysis using whole mount in situ hybridization and histological sectioning. These studies show that the mutated gene product affects the node formation as well as primitive streak formation.