A New ENU-Induced Mutant Mouse with Defective Spermatogenesis Caused by a Nonsense Mutation of the Syntaxin 2/Epimorphin (Stx2/Epim) Gene

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概要

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• Repro34 is an N-ethyl-N-nitrosourea (ENU)-induced mutation in mice showing male-specific infertility caused by defective spermatogenesis. In the present study, we investigated pathogenesis and molecular lesions in relation to spermatogenesis in the repro34/repro34 homozygous mouse. Histological examination of the testis showed that the seminiferous epithelium of the repro34/repro34 mouse contained spermatogonia and spermatocytes but no round and elongating spermatids. Instead of these haploid cells, multinucleated giant cells occupied the niche of the seminiferous tubules. Immunohistochemical staining for Hsc70t, an elongating spermatid specific protein, confirmed the absence of elongating spermatids. Furthermore, RT-PCR showed that there were significantly reduced expressions of the marker genes specifically expressed in the spermatid and that there was no difference in the expressions of the spermatocyte specific marker genes. These findings indicated interruption of the spermatogenesis during transition from the spermatocyte to spermatid in the repro34/repro34 mouse. The repro34 locus has been mapped on a 7.0-Mb region of mouse chromosome 5 containing the Syntaxin 2/Epimorphin (Stx2/Epim) gene, and targeted disruption of this gene has been reported to cause defective spermatogenesis. We therefore sequenced the entire coding region of the Stx2/Epim gene and found a nucleotide substitution that results in a nonsense mutation of this gene. The expression pattern of the Stx2/Epim gene during the first wave of spermatogenesis, increased expression at later stages of spermatogenesis, was in agreement with the affected phase of spermatogenesis in the adult repro34/repro34 testis. We therefore concluded that the male infertility of the repro34/repro34 mouse is caused by the interruption of spermatogenesis during transition from the spermatocyte to spermatid and that the nonsense mutation of the Stx2/Epim gene is responsible for the interruption of spermatogenesis.

• 2008-04-01

著者

• AKIYAMA Kouyou

  Graduate School of Natural Science and Technology, Okayama University

• KUNIEDA Tetsuo

  Graduate School of Natural Science and Technology, Okayama University

• NOGUCHI Junko

  Reproductive Biology Research Unit, National Institute of Agrobiological Sciences

• Akiyama Kouyou

  Graduate School Of Natural Sci. And Technol. Okayama Univ.

• Kunieda T

  Graduate School Of Natural Science And Technology Okayama University

• Kunieda Tetsuo

  Graduate School Of Natural Sci. And Technol. Okayama Univ.

• TSUJI Takehito

  Graduate School of Natural Science and Technology, Okayama University

• Noguchi J

  Division Of Animal Sciences National Institute Of Agrobiological Sciences

• Noguchi Junko

  Positron Medical Center Tokyo Metropolitan Institute Of Gerontology

• AKIMARU Shiho

  Graduate School of Natural Science and Technology, Okayama University

• ASANO Yuka

  Graduate School of Natural Science and Technology, Okayama University

• KHALAI Maryam

  Graduate School of Natural Science and Technology, Okayama University

• KIYOSU Chiyo

  Graduate School of Natural Science and Technology, Okayama University

• MASOUDI Ali

  Graduate School of Natural Science and Technology, Okayama University

• TAKAHASHI Sakino

  Tokyo University of Agriculture and Technology

• KATAYAMA Kentaro

  Graduate School of Natural Science and Technology, Okayama University

• Noguchi Junko

  Reproductive Biology Research Unit Division Of Animal Sciences National Institute Of Agrobiological

• Asano Yuka

  Graduate School Of Natural Sci. And Technol. Okayama Univ.

• Masoudi Ali

  Graduate School Of Natural Science And Technology Okayama University

• Kiyosu Chiyo

  Graduate School Of Natural Science And Technology Okayama University

• Akimaru Shiho

  Graduate School Of Natural Science And Technology Okayama University

• Khalaj Maryam

  Graduate School Of Natural Science And Technology Okayama University

• Tsuji T

  Graduate School Of Natural Sci. And Technol. Okayama Univ.

• Tsuji Takehito

  Graduate School Of Natural Science And Technology Okayama University

• Akiyama K

  Graduate School Of Natural Sci. And Technol. Okayama Univ.

• Katayama Kentaro

  岡山大学 大学院自然科学研究科

• Takahashi Sakino

  Tokyo Univ. Of Agriculture And Technol.

• KUNIEDA Tetsuo

  Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan

• NOGUCHI Junko

  Reproductive Biology Research Unit (Kannondai), Division of Animal Sciences, National Institute of Agrobiological Sciences

• KUNIEDA Tetsuo

  Graduate School of Environmental and Life Science, Okayama University

• TSUJI Takehito

  Graduate School of Environmental and Life Science, Okayama University

関連論文

• A New ENU-Induced Mutant Mouse with Defective Spermatogenesis Caused by a Nonsense Mutation of the Syntaxin 2/Epimorphin (Stx2/Epim) Gene
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