The ancestral gene for transcribed, low-copy repeats in the Prader-Willi/Angelman region encodes a large protein implicated in protein trafficking, which is deficient in mice with neuromuscular and spermiogenic abnormalities
The ancestral gene for transcribed, low-copy repeats in the Prader-Willi/Angelman region encodes a large protein implicated in protein trafficking, which is deficient in mice with neuromuscular and spermiogenic abnormalities
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DOI：
10.1093/hmg/8.3.533
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发表时间：
1999-03-01
影响因子：
3.5
通讯作者：
Nicholls, RD
中科院分区：
文献类型：
--
作者：
Ji, YG;Walkowicz, MJ;Nicholls, RD
转录的低拷贝重复元件与Prader-Willi和Angelman综合征中常见缺失的断点区域相关我们在这里报告的祖先基因（HERC 2）和一个家庭的重复，截短的副本，包括这些低拷贝重复序列的鉴定，该基因编码一个高度保守的巨大蛋白，HERC 2，这是一个遥远的相关p532（HERC 1），鸟嘌呤核苷酸交换因子（GEF）参与囊泡运输，小鼠基因组含有一个单一的HERC 2基因座，位于染色体7 C的jdf 2（juvenile development and fertility-2）区间，我们已经在三个独立的Nethyl-N-亚硝基脲诱导的jdf 2突变等位基因中鉴定了Herc 2中的单核苷酸剪接点突变，每个突变导致外显子跳跃，伴随翻译的过早终止和/或保守氨基酸的缺失。因此，Herc 2突变导致神经肌肉分泌囊泡和精子顶体缺陷，其他发育异常和jdf 2小鼠的幼年致死性。结合，这些研究结果表明，HERC 2是一个重要的基因编码的GEF参与蛋白质运输和降解途径的细胞。
Transcribed, low-copy repeat elements are associated with the breakpoint regions of common deletions in Prader-Willi and Angelman syndromes. We report here the identification of the ancestral gene (HERC2) and a family of duplicated, truncated copies that comprise these low-copy repeats, This gene encodes a highly conserved giant protein, HERC2, that is distantly related to p532 (HERC1), a guanine nucleotide exchange factor (GEF) implicated in vesicular trafficking, The mouse genome contains a single Herc2 locus, located in the jdf2 (juvenile development and fertility-2) interval of chromosome 7C, We have identified single nucleotide splice junction mutations in Herc2 in three independent Nethyl-N-nitvosourea-induced jdf2 mutant alleles, each leading to exon skipping with premature termination of translation and/or deletion of conserved amino acids. Therefore, mutations in Herc2 lead to the neuromuscular secretory vesicle and sperm acrosome defects, other developmental abnormalities and juvenile lethality of jdf2 mice. Combined, these findings suggest that HERC2 is an important gene encoding a GEF involved in protein trafficking and degradation pathways in the cell.