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9 April 2008 TSPY Expression Is Variably Altered in Transgenic Mice with Testicular Feminization
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TSPY (testis-specific protein, Y-encoded) genes are expressed in premeiotic germ cells and round spermatids. The topology and timing of TSPY expression, and also its homology to members of the TTSN-family, suggest that TSPY is a proliferation factor for germ cells. There is also evidence for a role of TSPY in the aetiology of testis cancer. TSPY is a candidate for GBY, the elusive gonadoblastoma locus on the human Y chromosome, which is thought to predispose dysgenetic gonads of 46, XY sex-reversed females to develop gonadoblastoma. We have previously generated a TSPY transgenic mouse line (Tg(TSPY)9Jshm) that carries approximately 50 copies of the human TSPY gene on the mouse Y chromosome. In order to elucidate TSPY expression under complete androgen insensitivity and to investigate a possible role of TSPY in gonadal tumorigenesis, we have now generated sex-reversed TSPY transgenic ArTfm mice hemizygous for the X-linked testicular feminization mutation (ArTfm). We can show that the TSPY transcript is aberrantly spliced in the testes of TSPY-ArTfm mice, and that TSPY expression is upregulated by androgen insensitivity in some but not all animals. TSPY transgenic mice showed significantly increased testes weights. In one TSPY transgenic ArTfm animal, spermatogenesis proceeded beyond meiotic prophase. No tumors of germ cell origin were found in the testes of TSPY-ArTfm mice. Five out of 46 TSPY transgenic ArTfm mice, and 3 out of 31 age-related NMRI-ArTfm controls developed Leydig cell tumors, whereas none of the age-matched ArTfm mice (n = 44) on a wild type background were affected by Leydig cell tumorigenesis.

Received: 5 December 2007; Accepted: 1 March 2008; Published: 9 April 2008

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