Characterization of the vertebral mutation, TgN370(Imusd)Rpw and the homologous human gene for the TgN737(Imorpk)Rpw polycystic kidney mouse mutation

The molecular analysis of mutations in the mouse is an ideal way of establishing structure-function relationships among individual genes, complex developmental phenotypes, and human diseases. We have identified and analyzed, as part of a large scale mutatgenesis program, two recessive insertional mutations in our TgN370(Imusd)Rpw (abbreviated TgN370Rpw) and TgN737(Imorpk)Rpw (abbreviated TgN737Rpw) lines. The TgN370Rpw mutation causes a novel "kinky tail" phenotype showing undulations of the distal spine, while the TgN737Rpw line exhibits a number of defects including polycystic kidneys, hepatic portal fibrosis, and polydactyly. We have cloned, characterized, and mapped both insertional mouse mutations and their corresponding human loci in an effort to describe developmentally important genes. This work demonstrates the usefulness of generating, characterizing, and cloning insertional mutations in the mouse, which can be applied to understanding gene function associated with the development of human diseases.