title: TSPY expression is variably altered in transgenic mice with testicular feminization.
abstract: 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 Ar(Tfm) mice hemizygous for the X-linked testicular feminization mutation (Ar(Tfm)). We can show that the TSPY transcript is aberrantly spliced in the testes of TSPY-Ar(Tfm) 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 Ar(Tfm) animal, spermatogenesis proceeded beyond meiotic prophase. No tumors of germ cell origin were found in the testes of TSPY-Ar(Tfm) mice. Five out of 46 TSPY transgenic Ar(Tfm) mice, and 3 out of 31 age-related NMRI-Ar(Tfm) controls developed Leydig cell tumors, whereas none of the age-matched Ar(Tfm) mice (n=44) on a wild type background were affected by Leydig cell tumorigenesis.
authors.affiliation: Institute of Human Genetics, Hannover Medical School, D-30625 Hannover, Germany. schubert.steffi@mh-hannover.de
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schubert
authors.forename: Kenji
authors.initials: K
authors.lastname: Kamino
authors.forename: Detlef
authors.initials: D
authors.lastname: Böhm
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Adham
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
authors.forename: Reinhard
authors.initials: R
authors.lastname: von Wasielewski
authors.forename: Darius
authors.initials: D
authors.lastname: Moharregh-Khiabani
authors.forename: Grazia
authors.initials: G
authors.lastname: Mauceri
authors.forename: Bernhard
authors.initials: B
authors.lastname: Vaske
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
authors.forename: Anja
authors.initials: A
authors.lastname: Schöner
authors.forename: Daniela
authors.initials: D
authors.lastname: Gonzalez-Fassrainer
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004351:Drug Resistance / Q000235:genetics; D005262:Feminization / Q000235:genetics*; D005786:Gene Expression Regulation; D006965:Hyperplasia / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013736:Testicular Neoplasms / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D019076:Transgenes
chemical_list: D000728:Androgens; D018797:Cell Cycle Proteins; C497749:TSPY1 protein, human