| Project/Area Number |
13470343
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
ISHIKAWA Mutsuo Asahikawa Medical College, Dept.of OB/GYN, Associate Professor, 医学部, 教授 (20002131)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Toshinobu Asahikawa Medical College, Dept.of OB/GYN, Staff, 医学部, 助手 (70360998)
TAKUMA Naoyuki Asahikawa Medical College, Dept.of OB/GYN, Associate Professor, 医学部, 助教授 (10312464)
YAMASHITA Tsuyoshi Asahikawa Medical College, Dept.of OB/GYN, Staff, 医学部, 講師 (30271787)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2001: ¥10,400,000 (Direct Cost: ¥10,400,000)
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| Keywords | LHX / Development / Homeobox gene / Mbx / SYCP3 / Azoospermia / LIM / 流産 / 奇形 / ホメオボックス / 小眼症 / 遺伝子発現 / 発生 / 悪性腫瘍 |
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| Research Abstract |
BACKGROUND : Many cases of male infertility are diagnosed as idiopathic, reflecting poor understanding of the molecular defects underlying the abnormality. As more gene mutations causing male infertility in mice become known, there are improving prospects that knowledge about the genetic aetiology of human male infertility can be expanded. Sycp3 encodes a component of the synaptonemal complex A null mutation of Sycp3 in mice causes azoospermia with meiotic arrest. We tested the hypothesis that mutation of the human testis-specific SYCP3 is associated with human non-obstructive azoospermia.
METHODS : Human SYCP3 was isolated on the basis of homology between mouse Sycp3 cDNA and human genome sequences at the aminoacid level. Tissue-specific expression of SYCP3 was analysed by PCR of human cDNA. Samples of DNA from 19 azoospermic patients with maturation arrest and 75 normal fertile control men were screened for mutations in the SYCP3 gene by sequence analysis of the gene. The functional significance of the mutations found was analysed by a protein interaction study of the wild-type and truncated SYCP3 proteins.
FINDINGS : We identified in two patients a 1 bp deletion (643delA) that results in a premature stop codon and truncation of the C-terminal, coiled-coil-forming region of the SYCP3 protein. The mutant protein showed greatly reduced interaction with the wild-type protein in vitro and interfered with SYCP3 fibre formation in cultured cells.
INTERPRETATION : We suggest that SYCP3 has an essential meiotic function in human spermatogenesis that is compromised by the mutant protein via dominant negative interference.
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