Infertility Associated with Meiotic Failure in the tremor Rat (tm/tm) is Caused by the Deletion of Spermatogenesis Associated 22
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概要
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The tremor rat is an autosomal recessive mutant exhibiting sterility with gonadal hypoplasia in both sexes. The causative mutation tremor (tm) is known as a genomic deletion spanning >200 kb in Chr 10q24. Spermatogenesis associated 22 (Spata22) has been shown to be a vertebrate-specific gene essential for the progression of meiosis through prophase I and completion of chromosome synapsis and meiotic recombination using a mouse repro42 mutant carrying an N-ethyl-N-nitrosourea (ENU)-induced nonsense mutation in Spata22. In this study, we show that Spata22 was identified as the gene responsible for the failure of gametogenesis to progress beyond meiosis I in tm homozygous rats by a transgenic rescue experiment. Meiosis was arrested during prophase I in the mutant testis. Precise mapping of the breakage point revealed that the deleted genomic region spanned approximately 240 kb and comprised at least 13 genes, including Spata22. Rat Spata22 was predominantly expressed in the testis, and its transcription increased with the first wave of spermatogenesis, as seen in the mouse ortholog. These results suggest that Spata22 may play an important role in meiotic prophase I in rats, as seen in mice, and that the tm homozygous rat may be useful for investigating the physiological function of Spata22, as an experimental system for clarifying the effect of a null mutation, and may be an animal model for studying the pathogenesis and treatment of infertility caused by impaired meiosis.
著者
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Serikawa Tadao
Institute For Laboratory Animals Faculty Of Medicine Kyoto University
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Inui Toshihide
Mitsubishi Tanabe Pharma Co., Ltd., 2-6-18, Kitahama, Chuo-ku, Osaka 541-8505, Japan
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Kitada Kazuhiro
Division of Bioscience, Graduate School of Science, Hokkaido University, North 10 West 8, Kita-ku, Sapporo 060-0810, Japan
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Matsuda Yoichi
Laboratory of Animal Genetics, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya Aichi 464-8601, Japan
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ISHISHITA Satoshi
Division of Bioscience, Graduate School of Environmental Earth Science, Hokkaido University, North 10 West 8, Kita-ku, Sapporo 060-0810, Japan
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MATSUDA Youichi
Laboratory of Animal Genetics, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya Aichi 464-8601, Japan
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