Sperm dysfunction in the Rb(6.16)- and Rb(6.15)-bearing mice revisited: involvement of Hyalp1 and Hyal5.
Sperm dysfunction in the Rb(6.16)- and Rb(6.15)-bearing mice revisited: involvement of Hyalp1 and Hyal5.
复制标题
重新审视 Rb(6.16) 和 Rb(6.15) 携带小鼠的精子功能障碍：Hyap1 和 Hyal5 的参与。
DOI：
10.1002/mrd.20360
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发表时间：
2005
影响因子：
2.5
通讯作者：
Martin-Deleon,PatriciaA
中科院分区：
文献类型：
--
作者：
Zhang,Hong;Shertok,Stacy;Miller,Kimberly;Taylor,Leslie;Martin-Deleon,PatriciaA
先前我们发现精子粘附分子1（Spam1）是研究得最好的精子透明质酸酶，参与了与罗伯逊易位（Rb）相关的精子功能障碍。这种功能障碍导致纯合子Rb（6.16）或杂合子雄性Rb（6.15）易位和传递比畸变（TRD）小鼠的生育能力降低。这一结论是基于以下发现：Rbs中的spam1包含多点突变和位点的基因组改变[在Rb（6.16）的情况下]；并且伴随着RNA和蛋白质稳态水平的降低。在这里，我们发现小鼠6号染色体上透明质酸酶基因簇中紧密相连的家族成员hyalp1和hyal5在这些Rbs中也有点突变，导致两种编码蛋白的非保守性替换。为了验证spam1本身是否能够产生TRD，我们分析了该基因的野生型和零等位基因在携带者后代中的传播，结果表明没有显著的TRD。在无基因携带者中，TRD的缺失证明了在携带Rb的小鼠中，spam1只在TRD中起促进作用，并支持了Hyalp1和/或Hyal5参与精子功能障碍和由此产生的TRD。有人提出，这三个基因中点突变的聚类是自发突变的累积效应，由于Rb连接处发生的重组受到抑制，自发突变不会在群体中分散。摩尔。天线转换开关。Dev.©2005 Wiley‐Liss, Inc。
Earlier we showed thatSperm adhesion molecule1(Spam1), the best studied sperm hyaluronidase, is involved in the sperm dysfunction associated with Robertsonian translocations (Rb). The dysfunction results in reduced fertility in mice homozygous for the Rb(6.16) or the Rb(6.15) translocation and transmission ratio distortion (TRD) in heterozygous males. This conclusion was based on the finding thatSpam1in the Rbs harbors multiple point mutations and a genomic alteration at the locus [in the case of Rb(6.16)]; and is accompanied by reduced steady‐state levels of the RNA and protein. Here we show that closely linked family members in the hyaluronidase gene cluster on mouse chromosome 6,Hyalp1andHyal5, also harbor point mutations in these Rbs, leading to nonconservative substitutions in both the encoded proteins. To test ifSpam1by itself is capable of producing TRD we analyzed the transmission of wild‐type and null alleles of the gene in the progeny of carriers and show that there is no significant TRD. This lack of TRD in null carriers argues for only a contributory role ofSpam1in the TRD seen in the Rb‐bearing mice, and supports the involvement of Hyalp1 and/or Hyal5 in the sperm dysfunction and the resulting TRD. It is proposed that the clustering of point mutations in all three genes results from the cumulative effect of spontaneous mutations that do not disperse in the population due to suppression of recombination that occurs at Rb junctions. Mol. Reprod. Dev. © 2005 Wiley‐Liss, Inc.