Inherited sex reversal in mice: identification of a new primary sex-determining gene

Abstract

We present evidence that the inbred mouse strain C57BL/6J (B6) differs from Mus domesticus (DOM) at a locus involved in gonad determination and development as well as at the testis-determining locus on the Y chromosome (Tdy). This newly identified gene is named testis-determining, autosomal-1 (tda-1). Although the inheritance of tda-1 suggests it is located on an autosome, its location on the X and Y chromosome in their pairing-recombination region is not excluded. When mice are homozygous for the C57BL/6J-derived tda-1 allele (tda-1B6) and carry the Y chromosome from M. domesticus, they develop as true hermaphrodites or, more rarely, as females. In contrast, when they are homozygous Tda-1DOM/Tda-1DOM or heterozygous Tda-1/DOMtda-1B6 and carry a B6-derived or M. domesticus-derived Y chromosome they develop as normal males. A simple genetic model is presented that integrates proposed steps in gonad determination and the results from genetic experiments reported here. In addition, arguments are presented for the existence of an ovary-determining gene.