Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation.
Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation.
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Rb(6.16) 或 Rb(6.15) 易位小鼠的 Spam1 (PH-20) 突变和精子功能障碍。
DOI：
10.1007/s00335-001-1008-3
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
Martin-DeLeon,PA
中科院分区：
文献类型：
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作者：
Zheng,Y;Deng,X;Zhao,Y;Zhang,H;Martin-DeLeon,PA
在携带 Rb(6.16) 或 Rb(6.15) 罗伯逊易位 (Rb) 的小鼠中，与 Rb 相关的精子功能障碍已被证明会导致杂合子中的传输比扭曲 (TRD)。 TRD 的严重程度与精子粘附分子 1 (Spam1) 基因表达改变的严重程度直接相关，该基因映射到易位连接点附近的近端小鼠 6 号染色体 (Chr 6)，并编码具有透明质酸酶活性的精子抗原。在这里，我们证明，根据窝产仔数，Rb 纯合子的生育力显着降低 (P< 0.001)；并且通过精子选择渗透测定，携带 Rb 的精子的透明质酸渗透率显着降低 (P< 0.02–0.001)。催化动力学研究表明，Rb(6.15) 小鼠中 Spam1 (PH-20) 透明质酸酶活性降低是由于定性缺陷所致，而对于 TRD 较大的 Rb(6.16)，Spam1 存在定性和定量缺陷（经 Western 分析证实）。六个点突变聚集在 Rb(6.15) 的 Spam1 透明质酸结合域中。对于在 Spam1 位点具有总体基因组改变的 Rb(6.16)，11 个点突变分散在 5' 和 3' UTR 以及编码区，其中一个导致保守残基的替换。由于 Rb 连接附近的重组抑制，自发性 Spam1 突变的捕获被认为是精子功能障碍的主要潜在缺陷。
In mice bearing the Rb(6.16) or Rb(6.15) Robertsonian translocation (Rb), sperm dysfunction associated with the Rbs has been shown to lead to transmission ratio distortions (TRDs) in heterozygotes. The severity of the TRDs is directly related to the severity in the alteration of expression of the gene for the Sperm Adhesion Molecule 1 (Spam1), which maps to proximal mouse Chromosome 6 (Chr 6) near the translocation junction and encodes a sperm antigen with hyaluronidase activity. Here we demonstrate that there is a significantly reduced fertility in the Rb homozygotes (P< 0.001), based on litter size; and that with the Sperm Select Penetration assay Rb-bearing sperm have significantly decreased (P< 0.02–0.001) rates of penetration of hyaluronic acid. Catalytic kinetics studies indicate that reduced Spam1 (PH-20) hyaluronidase activity in the Rb(6.15) mice results from a qualitative defect, while for Rb(6.16) with the greater TRD both a qualitative and a quantitative deficiency (confirmed by Western analysis) of Spam1 exist. Six point mutations were shown to be clustered in the Spam1 hyaluronic acid-binding domain in Rb(6.15). For Rb(6.16) which has a gross genomic alteration at theSpam1locus, 11 point mutations are scattered in the 5′ and 3′ UTRs and the coding region, where one leads to the replacement of a conserved residue. Entrapment of spontaneousSpam1mutations, owing to recombination suppression near the Rb junctions, is proposed as the major underlying defect of the sperm dysfunction.