Originally published as Genetics Published Articles Ahead of Print on October 16, 2004.

Genetics, Vol. 169, 285-299, January 2005, Copyright © 2005
doi:10.1534/genetics.104.034967

Mutation of l7Rn3 Shows That Odz4 Is Required for Mouse Gastrulation

Amy C. Lossie1, Hisashi Nakamura1, Sharon E. Thomas2 and Monica J. Justice3

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030

3 Corresponding author: Department of Molecular and Human Genetics, Baylor College of Medicine, S413, Houston, TX 77030.
E-mail: mjustice{at}bcm.tmc.edu

A mouse homolog of the Drosophila pair-rule gene Odd Oz (Odz4) maps to the critical region of the l7Rn3 locus on mouse chromosome 7. Here we show that Odz4 is an excellent candidate for this allelic series because (1) it spans the entire critical region, (2) the phenotypes correlate with embryonic expression, (3) the complex genetic inheritance of the alleles is consistent with complex transcriptional regulation, and (4) one allele has a mutation in a conserved amino acid. Odz4 uses five alternate promoters that encode both secreted and membrane-bound proteins. Intragenic complementation of the l7Rn3 alleles is consistent with these multiple-protein isoforms. Further, the allelic series shows that Odz4 is required to establish the anterior-posterior axis of the gastrulating mouse embryo and is necessary later for mesoderm-derived tissues such as somites, heart, and skeleton. Sequencing of RT-PCR products from five of the six alleles reveals a nonconservative amino acid change in the l7Rn3m4 allele. This amino acid is important evolutionarily, as it is conserved to Drosophila. Together, our data indicate that Odz4 is mutated in the l7Rn3 allele series and performs roles in the mouse brain, heart, and embryonic patterning similar to those of its Drosophila counterpart.