A new large animal model of CLN5 neuronal ceroid lipofuscinosis in Borderdale sheep is caused by a nucleotide substitution at a consensus splice site (c.571+1G > A) leading to excision of exon 3
A new large animal model of CLN5 neuronal ceroid lipofuscinosis in Borderdale sheep is caused by a nucleotide substitution at a consensus splice site (c.571+1G > A) leading to excision of exon 3
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DOI：
10.1016/j.nbd.2007.09.006
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发表时间：
2008-02-01
影响因子：
6.1
通讯作者：
Palmer, David N.
中科院分区：
文献类型：
--
作者：
Frugier, Tony;Mitchell, Nadia L.;Palmer, David N.
巴顿病（神经性ceroid lipofuscinoses， NCLs）是一组遗传性儿童疾病，可导致严重的脑萎缩、失明和癫痫发作，导致过早死亡。到目前为止，已经确定了八种不同的基因，每种基因都与不同的形式有关。连锁分析表明，在受影响的新西兰Borderdale羊群体中存在CLN5形式。测序。研究证实，致病突变是一致剪接位点（c.571+1G> a）的替换，导致外显子3的切除和推测蛋白的截短。一种基于切除外显子3的分子诊断测试已经被开发出来。序列比对支持基因产物是可溶性溶酶体蛋白。分离储存体的Western blotting显示线粒体ATP合酶亚基c的特异性储存。这个群体正在扩大，作为机械研究和试验治疗的大型动物模型。(C) 2007爱思唯尔公司版权所有。
Batten disease (neuronal ceroid lipofuscinoses, NCLs) are a group of inherited childhood diseases that result in severe brain atrophy, blindness and seizures, leading to premature death. To date, eight different genes have been identified, each associated with a different form. Linkage analysis indicated a CLN5 form in a colony of affected New Zealand Borderdale sheep. Sequencing. studies established the disease-causing mutation to be a substitution at a consensus splice site (c.571+1G>A), leading to the excision of exon 3 and a truncated putative protein. A molecular diagnostic test has been developed based on the excision of exon 3. Sequence alignments support the gene product being a soluble lysosomal protein. Western blotting of isolated storage bodies indicates the specific storage of subunit c of mitochondrial ATP synthase. This flock is being expanded as a large animal model for mechanistic studies and trial therapies. (C) 2007 Elsevier Inc. All rights reserved.