Dmrt1 is required for mammalian testis differentiation
In the October issue of Genes & Development, Christopher Raymond and colleagues detail their discovery that the gene, Dmrt1, is essential for normal mammalian testis development. This work provides the first functional evidence that Dmrt1 is required for male sexual development in vertebrates, and helps elucidate the basis of human testicular degeneration syndrome.
The Dmrt1 gene has for many years been a candidate for human testis dysgenesis, a disease characterized by severely defective testicular development. Although Dmrt1 maps to the position on chromosome 9 which is deleted in these patients, no definitive data has been able to link the gene and the disease. Until now.
Raymond and colleagues made knockout mice which harbor a mutated form of Dmrt1. These Dmrt1 mutants failed to undergo postnatal testis differentiation. The resulting phenotype of extremely small adult testis, seminiferous tubule disorganization, germ cell death and sterility is similar to the abnormal testicular development found in human men with testis dysgenesis syndrome. Mutations in Dmrt1 do not adversely affect female ovary development.
In addition to lending insight into the basis of human testis dysgenesis syndrome, Raymond's finding has surprising evolutionary implications. Proteins similar to Dmrt1 are known to be involved in male sexual development in insects and worms. Therefore, Dmrt1 is the first evidence of molecular conservation in the dramatically divergent pathways of sex determination between vertebrates and invertebrates.
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Christopher S. Raymond's colleagues are: Mark W. Murphy, M. Gerard O'Sullivan, Vivian J. Bardwell, and David Zarkower
Genes & Development