INVERSIN, A NOVEL GENE IN THE VERTEBRATE LEFT-RIGHT AXIS PATHWAY, IS PARTIALLY DELETED IN THE INV MOUSE

Visceral left-right asymmetry occurs in all vertebrates, but the inver sion of embryo turning (inv) mouse, which resulted following a random transgene insertion, is the only model in which these asymmetries are consistently reversed(1). We report positional cloning of the gene und erlying this recessive phenotype. Although transgene insertion was acc ompanied by neighbouring deletion and duplication events(1,2), our YAC phenotype rescue studies indicate that the mutant phenotype results f rom the deletion. After extensively characterizing the 47-kb deleted r egion and flanking sequences from the wild-type mouse genome, we found evidence for only one gene sequence in the deleted region. We determi ned the full-length 5.5-kb cDNA sequence and identified 16 exons, of w hich exons 3-11 were eliminated by the deletion, causing a frameshift. The novel gene specifies a 1062-aa product with tandem ankyrin-like r epeat sequences. Characterization of complementing and non-complementi ng YAC transgenic families revealed that correction of the inv mutant phenotype was concordant with integration and intact expression of thi s novel gene, which we have named inversin (Invs).