Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta.
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.
Nakamura
Takahisa
T
Division of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Yao
Ryoji
R
Ogawa
Takehiko
T
Suzuki
Toru
T
Ito
Chizuru
C
Tsunekawa
Naoki
N
Inoue
Kimiko
K
Ajima
Rieko
R
Miyasaka
Takashi
T
Yoshida
Yutaka
Y
Ogura
Atsuo
A
Toshimori
Kiyotaka
K
Noce
Toshiaki
T
Yamamoto
Tadashi
T
Noda
Tetsuo
T
D000818:Animals; D019556:COS Cells; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D005347:Fibroblasts; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009845:Oligospermia / Q000150:complications* / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology; D012671:Seminiferous Tubules / Q000378:metabolism; D013081:Sperm Motility; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000002:abnormalities*; D033581:Stem Cell Transplantation
D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C061606:Rxrb protein, mouse; D019009:Proto-Oncogene Proteins c-kit