Originally published as Genetics Published Articles Ahead of Print on May 5, 2008.

Genetics, Vol. 179, 419-427, May 2008, Copyright © 2008
doi:10.1534/genetics.108.088088

The Chromosome 11 Region From Strain 129 Provides Protection From Sex Reversal in XY^POS Mice

Ganka Nikolova^*, Janet S. Sinsheimer^*,, Eva M. Eicher and Eric Vilain^*,,1

^* Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, Departments of Biostatistics and Biomathematics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, Departments of Pediatrics and Urology, David Geffen School of Medicine, University of California, Los Angeles, California 90095 and The Jackson Laboratory, Bar Harbor, Maine 04609

¹ Corresponding author: Department of Human Genetics, David Geffen School of Medicine, Gonda Center, Room 5506, 695 Charles Young Dr. S., University of California, Los Angeles, CA 90095-7088.
E-mail: evilain{at}ucla.edu

C57BL/6J (B6) mice containing the Mus domesticus poschiavinus Y chromosome, Y^POS, develop ovarian tissue, whereas testicular tissue develops in DBA/2J or 129S1/SvImJ (129) mice containing the Y^POS chromosome. To identify genes involved in sex determination, we used a congenic strain approach to determine which chromosomal regions from 129Sl/SvImJ provide protection against sex reversal in XY^POS mice of the C57BL/6J.129-Y^POS strain. Genome scans using microsatellite and SNP markers identified a chromosome 11 region of 129 origin in C57BL/6J.129-Y^POS mice. To determine if this region influenced testis development in XY^POS mice, two strains of C57BL/6J-Y^POS mice were produced and used in genetic experiments. XY^POS adults homozygous for the 129 region had a lower incidence of sex reversal than XY^POS adults homozygous for the B6 region. In addition, many homozygous 129 XY^POS fetuses developed normal-appearing testes, an occurrence never observed in XY^POS mice of the C57BL/6J-Y^POS strain. Finally, the amount of testicular tissue observed in ovotestes of heterozygous 129/B6 XY^POS fetuses was greater than the amount observed in ovotestes of homozygous B6 XY^POS fetuses. We conclude that a chromosome 11 locus derived from 129Sl/SvImJ essentially protects against sex reversal in XY^POS mice. A number of genes located in this chromosome 11 region are discussed as potential candidates.

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