International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Zheng L, Nakamura H, Lossie A, Jafar-Nejad H, Schulze K, Bellen H, Justice M

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States

ENU mutagenesis generated six mutant alleles at the mouse Odz4 locus. Five of the six alleles cause early embryonic lethality, while the sixth one demonstrates defects in skeletal and hematopoietic development. The Odz4 gene, also called ten-m4, encodes a 270kD transmembrane protein and is conserved among human, mouse and Drosophila. The Drosophila homologue was previously identified to be a pair-rule gene and was thought to be involved in a novel signal transduction pathway.

To elucidate the pathway, we set out to identify the interacting partners by both biochemical and genetic methods with the Drosophila gene (odz) as a starting point. 1) By performing yeast two hybrid screening, we have identified filamin that may physically interact with the odz protein. Filamin is an actin binding protein which is critical for ring canal formation during Drosophila oogenesis. The interacting part of odz, defined here as FID domain, has been determined by deletion mapping. The expression patterns of filamin and odz during embryonic development are partially overlapped. The mouse Odz4 and FilaminA also have overlapping expression at several embryonic stages. The biological significance of this possible interaction in embryonic and later developmental stages is currently under investigation in both Drosophila and mouse. 2) By characterizing several new odz alleles, we found that the odz gene was not a pair-rule gene. Instead, it causes defects in motor neuron axon routing. The segmental nerve b (SNb) does not innervate or innervate into unrelated muscles. We are currently generating odz cDNA transgenic flies to rescue the defects. This study on the biochemical and genetic interactions may partially reveal the important biological roles that odz plays during development.

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