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Letter
Nature Genetics  36, 528 - 533 (2004)
Published online: 25 April 2004; | doi:10.1038/ng1344

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

Takahisa Nakamura1, Ryoji Yao2, Takehiko Ogawa3, Toru Suzuki1, Chizuru Ito4, Naoki Tsunekawa5, Kimiko Inoue6, Rieko Ajima1, Takashi Miyasaka1, Yutaka Yoshida1, Atsuo Ogura6, Kiyotaka Toshimori4, Toshiaki Noce5, Tadashi Yamamoto1 & Tetsuo Noda2, 7, 8

1  Division of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.

2  Department of Cell Biology, Japanese Foundation for Cancer Research (JFCR) Cancer Institute, Tokyo 170-8455, Japan.

3  Department of Urology, School of Medicine, Yokohama City University, Kanagawa 236-0004, Japan.

4  Department of Anatomy and Developmental Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.

5  Mitsubishi Kagaku Institute of Life Sciences, Tokyo 194-8511, Japan.

6  RIKEN Bioresource Center, Ibaraki 305-0074, Japan.

7  Center for Translational and Advanced Animal Research on Human Disease, Tohoku University School of Medicine, Miyagi 980-8575, Japan.

8  Mouse Functional Genomics Research Group, RIKEN Genomic Sciences Center, Kanagawa 244-0804, Japan.

Correspondence should be addressed to Tadashi Yamamoto tyamamot@ims.u-tokyo.ac.jp or Tetsuo Noda tnoda@ims.u-tokyo.ac.jp
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 infertility1. Here we show that Cnot7-/- males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor2, 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)3. 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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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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