The A/HeJ mouse: a dysfunction in sex development

Robinson J1,2, Graham A1 and Kalitsis P1,2

  1. Murdoch Children’s Research Institute.
  2. University of Melbourne.

Expression of the mammalian Y chromosome gene, Sry, is the trigger for development of a testis in males. In mice, the action of this gene is tightly regulated in both space and time, following a distinctive wave pattern of expression across the gonad over a very brief window of embryonic development. Failure of Sry expression to adhere to this precise profile, by expression reduction or delay, can result in defects in the development of the gonad. This can present as sex reversal, producing an XY female, or in the development of a gonad which consists of both ovarian and testicular tissue (an ovotestis). The A/HeJ mouse strain has been previously shown to have a slight defect in testis determination, resulting in 4% of males developing as overtly intersex, and 17% having small testes which do not produce epididymal sperm. The cause of this developmental defect is unknown; we hypothesise that it is due to an interstitial deletion in a gene array lying between Sry and the Y chromosome centromere, exerting a positional effect on Sry. This study aims to determine the nature of this structural change on the A/HeJ Y chromosome, as well as characterise the epigenetic and gene expression changes to Sry that would exert the observed phenotype in this mouse strain.