Partial rescue of the KIT-deficient testicular phenotype in KitW-v/KitW-v Tg(TSPY) mice.
TSPY encodes the testis-specific protein Y-linked. In man, expression of TSPY is restricted to the testis, where TSPY is expressed in spermatogonia, primary spermatocytes, and round spermatids, and to the prostate gland. There is circumstantial evidence that TSPY is involved in spermatogonial proliferation and gonadal tumorigenesis. Because the laboratory mouse carries the Tspy gene in a naturally silenced state (Tspy-ps), we previously restored TSPY activity in mice and generated a TSPY transgenic mouse line in which the organization and expression of the human TSPY transgene follow the human pattern. In the present study, we generated TSPY transgenic KIT-deficient Kit(W-v)/Kit(W-v) mice and analyzed the histology of the testes and epididymides in order to contribute to understanding TSPY function in early germ cell development and spermatogenesis. The KIT receptor and its ligand KITL, previously called stem cell factor, have an indispensable role in hematopoiesis, melanogenesis, and gametogenesis. Homozygous Kit(W-v) mutant male mice on a C57BL/6J background with a mutation in the Kit gene are infertile due to an almost total loss of germ cells in the testes. In this study, histological analyses of testes and epididymides showed an increased number of meiotic and postmeiotic germ cells in Kit(W-v)/Kit(W-v) Tg(TSPY) mice compared with age-matched Kit(W-v)/Kit(W-v) controls. TSPY was able to restore fertility of some but not all TSPY transgenic Kit(W-v)/Kit(W-v) males. Our findings show that TSPY is able to partially rescue spermatogenesis and fertility of Kit(W-v)/Kit(W-v) mutants and thereby point to a putative role of TSPY in fetal and adult germ cell proliferation.
Institutes of Human Genetics and Biometry, Hannover Medical School, Hannover, Germany.
Anja
A
Schöner
Ibrahim
I
Adham
Grazia
G
Mauceri
Britta
B
Marohn
Bernhard
B
Vaske
Jörg
J
Schmidtke
Stephanie
S
Schubert
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004822:Epididymis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005298:Fertility; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011544:Pseudogenes / Q000235:genetics*; D013091:Spermatogenesis; D013737:Testis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*
D018797:Cell Cycle Proteins; D019009:Proto-Oncogene Proteins c-kit