ANALYSIS OF A CANDIDATE MOUSE IV (INVERSUS VISCERUM) GENE. • 123

Abstract

Inherited single gene defects have been identified in both mice and humans that result in the loss of control over the development of left-right asymmetry of the heart and viscera. In mice, the recessively inheritediv (inversus viscerum) mutation results in randomization of left-right asymmetry: 50% of homozygous, live-born iv mice have situs solitus and levocardia and 50% have situs inversus and dextrocardia. Previous work localizes the iv gene to the sub-telomeric 160 kB of mouse chromosome 12 within the immunoglobulin heavy chain locus. A candidateiv gene, c8 was found within the cloned DNA from the corresponding region of mouse chromosome 12. This candidate gene c8 shows significant homology to a cytoskeleton-associated phosphoprotein and shows evolutionary conservation with a high degree of homology to Xenopus and human clones. Northern blot analysis of whole mouse embryos demonstrates the onset of c8 expression during gastrulation and the termination of expression after cardiac loop formation. In adult mice, c8 is expressed in spleen, brain, and testis. Using in-situ hybridization in Xenopus embryos, c8 is expressed in heart, gut, and brain primordia (all asymmetric structures) from gastrulation through cardiac looping, but not during later stages of embryonic development.