CLONING OF INV, A GENE THAT CONTROLS LEFT RIGHT ASYMMETRY AND KIDNEY DEVELOPMENT/

Most vertebrate internal organs show a distinctive left/right asymmetr y. The inv (inversion of embryonic turning) mutation in mice was creat ed previously by random insertional mutagenesis(1); it produces both a constant reversal of left/right polarity (situs inversus) and cyst fo rmation in the kidneys(2). Asymmetric expression patterns of the genes nodal and lefty are reversed in the inv mutant(3-6), indicating that inv may act early in left/right determination. Here we identify a new gene located at the inv locus. The encoded protein contains 15 consecu tive repeats of an Ank/Swi6 motif(7,8) at its amino terminus. Expressi on of the gene is the highest in the kidneys and liver among adult tis sues, and is seen in presomite-stage embryos. Analysis of the transgen ic genome and the structure of the candidate gene indicate that the ca ndidate gene is the only gene that is disrupted in inv mutants. Transg enic introduction of a minigene encoding the candidate protein restore s normal left/right asymmetry and kidney development in the inv mutant , confirming the identity of the candidate gene.