Expression of a K48R mutant ubiquitin protects mouse testis from cryptorchid injury and aging.
Testis injury models can be useful for determining the in vivo function of genes. In this study, ubiquitin, a tag for 26S-proteasome degradation, was mutated at lysine 48 (K48R) to inhibit ubiquitin chain assembly. K48R transgenic mice had testes with delayed germ cell loss following the acute injury of experimental cryptorchidism, and were resistant to the chronic injury of aging-associated testicular atrophy. After 4 days of cryptorchid-mediated heat stress, the average weight of cryptorchid testes in wild-type ubiquitin mice was significantly lower (P < 0.05) than in K48R mutant ubiquitin mice, indicating that altered ubiquitination delayed germ cell death. Light microscopy confirmed that the testicular injury, in both wild-type and K48R ubiquitin mice, was due to germ cell death. In addition, wild-type ubiquitin mice aged 19 to 22 months showed greater testicular atrophy and decreased average seminiferous tubule diameter when compared with K48R-aged testes. These results demonstrate a resistance to testicular injury conferred by the K48R mutation, suggesting that ubiquitin-mediated protein degradation is involved in the processing or modulation of testicular insults.
Rasoulpour
Reza J
RJ
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA.
Schoenfeld
Heidi A
HA
Gray
Douglas A
DA
Boekelheide
Kim
K
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001120:Arginine / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D003456:Cryptorchidism / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D019610:Cytoprotection; D015870:Gene Expression; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013091:Spermatogenesis; D013094:Spermatozoa; D013737:Testis / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology; D019076:Transgenes; D025801:Ubiquitin / Q000378:metabolism*
D025801:Ubiquitin; D001120:Arginine; D008239:Lysine