Nkx3.1, a murine homolog of Drosophila bagpipe, regulates epithelial ductal branching and proliferation of the prostate and palatine glands

Nkx3.1 is a homeobox gene related to Drosophila bagpipe. Nkx3.1 is an early marker of the sclerotome and a subset of vascular:smooth muscle cells, and at later stages, this gene is expressed in the prostate, palatine glands, kidney, and restricted regions of the central nervous system. In the presen t study, we determined the chromosomal localization of Nkx3.1 and examined the function of Nkx3.1 in vivo by using gene targeting technique. Interesti ngly, Nkx3.1 mapped to the central region of the mouse chromosome 14 and wa s linked to Nkx2.6, a murine homolog of Drosophila tinman, Homozygous mutan t mice for Nkx3.1 were viable and:fertile, and the phenotype was, unexpecte dly, confined to the prostate and palatine glands. The homozygous mutant mi ce exhibited defective branching morphogenesis of the prostate and palatine glands. Moreover, epithelial cells of the mutant prostate and palatine gla nds showed significant hyperplasia, No abnormalities were detected in the s clerotome, blood vessels, kidney, or brain. These results indicate that Nkx 3.1 plays a critical role in epithelial branching and proliferation in the prostate and palatine glands. However, we did not observe prostate cancer i n homozygous mutant mice up to 2 years of age. Therefore, involvement of NK X3.1 in carcinogenesis in men needs to be carefully determined by further i nvestigation, Published 2000 Wiley-Liss, Inc.(dagger).