The mouse t complex distorter/sterility candidate, Dnahc8, expresses a gamma-type axonemal dynein heavy chain isoform confined to the principal piece of the sperm tail.
The mouse t complex distorter/sterility candidate, Dnahc8, expresses a gamma-type axonemal dynein heavy chain isoform confined to the principal piece of the sperm tail.
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小鼠 t 复合物扭曲/不育候选者 Dnahc8 表达局限于精子尾部主要部分的 γ 型轴丝动力蛋白重链亚型。
DOI：
10.1016/j.ydbio.2005.06.002
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发表时间：
2005
影响因子：
2.7
通讯作者：
Pilder,StephenH
中科院分区：
文献类型：
--
作者：
Samant,SadhanaA;Ogunkua,OlugbemigaO;Hui,Ling;Lu,Jing;Han,Yibing;Orth,JoanneM;Pilder,StephenH
雄性小鼠中t单倍型(T)的杂合性导致带有t的17号染色体同源物向其后代的扭曲传递(TRD)。然而，t的纯合性导致男性不育，从而限制了t在整个人群中的传播。依赖于钙离子的精子尾部弯曲表型“鱼钩”和“花体”分别与t相关的男性TRD和不育性状紧密相关。遗传学研究表明，Dnahc8基因t等位基因的纯合性是导致“Curlicue”表达的部分原因。Dnahc8是一种轴线型动力蛋白重链(γ-type dynein Heavy Chain，γ)基因，但它是否参与了“鱼钩”/Trd，目前尚不清楚。在这里，我们报道了DNAHC8的主要异构体在+/+和t/t动物的睾丸和精子中大量表达，携带一个延伸的N末端和全长的C末端，并且稳定且同样丰富。通过电子计算机分析，我们还证明在野生型DNAHC8的高度保守位置的17个突变中，至少有3个突变能够显著改变正常的DNAHC8功能。有趣的是，DNAHC8仅限于精子尾巴的主要部分。这项研究的综合结果提示了DNAHC8功能障碍和参与“花环”的可能机制，并支持“花环”是一个多基因现象的假说。他们还证明，+/t男性精子加速的“鱼钩”表型与DNAHC8t功能障碍没有直接联系。
Heterozygosity for a t haplotype (t) in male mice results in distorted transmission (TRD) of the t-bearing chromosome 17 homolog to their offspring. However, homozygosity for t causes male sterility, thus limiting the spread of t through the population at large. The Ca2+-dependent sperm tail curvature phenotypes, “fishhook”, where abnormally high levels of sperm exhibit sharp bends in the midpiece, and “curlicue”, where motile sperm exhibit a chronic negative curving of the entire tail, have been tightly linked to t-associated male TRD and sterility traits, respectively. Genetic studies have indicated that homozygosity for the t allele of Dnahc8, an axonemal γ-type dynein heavy chain (γDHC) gene, is partially responsible for expression of “curlicue”; however, its involvement in “fishhook”/TRD, if any, is unknown. Here we report that the major isoform of DNAHC8 is copiously expressed, carries an extended N-terminus and full-length C-terminus, and is stable and equally abundant in both testis and sperm from +/+ and t/t animals. By in silico analysis we also demonstrate that at least three of the seventeen DNAHC8tmutations at highly conserved positions in wild-type DHCs may be capable of substantially altering normal DNAHC8 function. Interestingly, DNAHC8 is confined to the principal piece of the sperm tail. The combined results of this study suggest possible mechanisms of DNAHC8tdysfunction and involvement in “curlicue”, and support the hypothesis that “curlicue” is a multigenic phenomenon. They also demonstrate that the accelerated “fishhook” phenotype of sperm from +/t males is not directly linked to DNAHC8tdysfunction.
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DOI：
--
发表时间：
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期刊：
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影响因子：
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DOI：
10.1073/pnas.81.12.3708
发表时间：
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