Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta
Copyright policy )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.
- RIKEN BioResource Center (BRC), Japan Japan
- Japanese Foundation For Cancer Research Japan
- Chiba University Japan
- Tohoku University Japan
- University of Tokyo Japan
Male, Mice, Knockout, Mice, Inbred BALB C, Chromosomal Proteins, Non-Histone, Mice, Nude, Oligospermia, Fibroblasts, Seminiferous Tubules, DNA-Binding Proteins, Mice, Inbred C57BL, Chromatin Assembly Factor-1, Mice, Proto-Oncogene Proteins c-kit, Phenotype, Gene Expression Regulation, COS Cells, Sperm Motility, Animals, Female, Spermatogenesis
Male, Mice, Knockout, Mice, Inbred BALB C, Chromosomal Proteins, Non-Histone, Mice, Nude, Oligospermia, Fibroblasts, Seminiferous Tubules, DNA-Binding Proteins, Mice, Inbred C57BL, Chromatin Assembly Factor-1, Mice, Proto-Oncogene Proteins c-kit, Phenotype, Gene Expression Regulation, COS Cells, Sperm Motility, Animals, Female, Spermatogenesis
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