Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

Takahisa Nakamura, Ryoji Yao, Takehiko Ogawa, Toru Suzuki, Chizuru Ito, Naoki Tsunekawa, Kimiko Inoue, Rieko Ajima, Takashi Miyasaka, Yutaka Yoshida, Atsuo Ogura, Kiyotaka Toshimori, Toshiaki Noce, Tadashi Yamamoto, Tetsuo Noda

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)528-533
Number of pages6
JournalNature Genetics
Volume36
Issue number5
DOIs
Publication statusPublished - 2004 May
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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