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

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.

• Authors: 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
• Journal: Nature genetics (Nat Genet) Vol. 36 Issue 5 Pg. 528-33 (May 2004) ISSN: 1061-4036 [Print] United States
• PMID: 15107851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin Assembly Factor-1
• Chromosomal Proteins, Non-Histone
• DNA-Binding Proteins
• Rxrb protein, mouse
• Proto-Oncogene Proteins c-kit

Topics

• Animals
• COS Cells
• Chromatin Assembly Factor-1
• Chromosomal Proteins, Non-Histone (genetics, physiology)
• DNA-Binding Proteins (genetics, physiology)
• Female
• Fibroblasts
• Gene Expression Regulation
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Nude
• Oligospermia (complications, etiology, genetics)
• Phenotype
• Proto-Oncogene Proteins c-kit (genetics, physiology)
• Seminiferous Tubules (metabolism)
• Sperm Motility
• Spermatogenesis (genetics)
• Spermatozoa (abnormalities)
• Stem Cell Transplantation