Cell Interactions in the Sex Organs of Sex Reversed Mice Heterozygous for Testicular Feminization

Abstract

The X-linked mutation for testicular feminization (Tfm) described by Lyon and Hawkes (1970) causes androgen insensitivity of the testosterone target cells. The molecular basis of the phenotype is a defect of the androgen receptor protein (Attardi and Ohno, 1974; Gehring and Tomkins, 1974). Due to random X inactivation, XX mice heterozygous for Tfm are mosaics with respect to androgen sensitivity. They can be converted to males by the autosomal dominant mutation for “sex reversal” (Sxr) described by Cattanach, Pollard, and Hawkes (1971). By imitating the Y-chromosome, Sxr induces formation of testes in XX embryos. The testosterone produced by the embryonic testes in turn induces formation of male sex organs. In sex-reversed embryos heterozygous for Tfm, testosterone encounters a mixed population of androgen-insensitive and androgen-sensitive cells. In the androgen-insensitive cells the X chromosome bearing Tfm is active. The Tfm cells express the defective receptor protein and therefore are constitutively bound to form female organs. In the androgen-sensitive cells the wild-type X is active. The wild-type cells therefore express an intact androgen receptor protein. They respond to testosterone and are bound to form male sex organs.