International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

G3 Male Sexual Development in the Absence of Sry

Bishop, C. E., Whitworth, D., Agoulnik, A., Harrison, W., Agoulnik I., Behringer, R., and Overbeek, P. Department of OB/GYN, Baylor College of Medicine, Houston, Texas

In mice the male sex determination switch is controlled by a single dominant gene on the Y chromosome, Sry. It is thought to act by triggering the development of the Sertoli cell lineage in the embryonic bipotential gonad. Sertoli cells in turn direct the differentiation of the remaining cell types in the testis. This switch in cell fate is thought to involve a complex interaction between a number of regulatory genes including Sox9, Sox3, Dax1 and Sf1. We report here a new mouse mutant, Odsex in which male development proceeds normally in XX mice despite the complete absence of the Y chromosome and Sry. It implicates Sox9 as a primary inducer of Sertoli cell development and is consistent with the repressor model of sex determination.

This mutant was first identified in a transgenic FVB strain carrying a tyrosinase minigene. An excess of males (~75%) led us to examine the genotypes of the offspring by PCR and karyotype. It was found that all XX mice carrying the transgene developed as phenotypically normal, although sterile males. High resolution banding analysis indicated that these mice have an apparently normal XX karyotype. Importantly, PCR analysis indicates that all known Y chromsome genes including Sry are completely absent. Meiotic mapping and FISH analysis place the transgene within 1cM of Sox9 on distal Chromosome 11. In situ and RT-PCR analysis show that Sox9 is correctly expressed in the developing XX transgenic male genital ridge and testis.

These data indicate that the transgene insertion has affected a critical element in the sex-determining pathway, bypassing Sry control. Our current model to explain these findings proposes that females normally synthesize repressors that inhibit Sox9 expression specifically in the embryonic female gonad. The repressors, which may include Dax1, Sox3 or Sf1, regulate gonad specific Sox-9 expression by binding to control elements at some distance from the gene. In normal males, expression of Sry interferes with the activity or binding of the repressor, allowing Sox9 to be expressed and the pathway of male development to ensue. In the Odsex family, the transgenic insertion has disrupted the repressor binding sites rendering them ineffective. This now allows gonadal expression of Sox9 in the absence of Sry producing sex reversed XX males. Further molecular characterization of this mutant is in progress.

 


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012