Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta.
Nat Genet
; 36(5): 528-33, 2004 May.
Article
em En
| MEDLINE
| ID: mdl-15107851
ABSTRACT
Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7(-/-) males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7(-/-) mice. Transplantation of spermatogonial stem cells from male Cnot7(-/-) mice to seminiferous tubules of Kit mutant mice (Kit(W/W-v)) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7(-/-) condition. The testicular phenotypes of Cnot7(-/-) mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligospermia
/
Motilidade dos Espermatozoides
/
Espermatozoides
/
Proteínas Cromossômicas não Histona
/
Regulação da Expressão Gênica
/
Proteínas de Ligação a DNA
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Japão