ROLE OF SUBUNIT-9 OF MITOCHONDRIAL ATP SYNTHASE IN BATTEN-DISEASE
ROLE OF SUBUNIT-9 OF MITOCHONDRIAL ATP SYNTHASE IN BATTEN-DISEASE
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DOI：
10.1002/ajmg.1320570250
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发表时间：
1995-06-05
期刊：
影响因子：
--
通讯作者：
BOUSTANY, RM
中科院分区：
文献类型：
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作者：
JOHNSON, DW;SPEIER, S;BOUSTANY, RM
线粒体ATP合酶亚基-9在Batten病中的作用通过表征编码该蛋白的基因在人体组织中的表达来定义。两种遗传学上不同的神经元蜡样脂褐质病（NCL）包括Batten病：晚期婴儿型（LINCL）和青少年型（JNCL）。我们测试了两种类型患者的细胞系和组织，沿着还有正常对照。发现病变和正常样品之间的mRNA和蛋白质表达的差异。在LINCL和JNCL组织中，以及在6个LINCL和5个JNCL成纤维细胞系中的4个中检测到亚基-9蛋白的抗体染色。在来自专性携带者、正常对照和6个其他胆积病对照的成纤维细胞中未观察到免疫反应性，除了C型尼曼-匹克细胞中的微弱染色。LINCL和JNCL之间的组织切片和成纤维细胞的染色模式存在明显差异。三个亚基-9转录本（Hum1，Hum2和Hum3），特别是在NCL和正常人体组织从心脏，肝脏，大脑，肌肉和胰腺中检测到。在Batten病中发现亚基-9基因的转录调控被改变。分离与每个亚基9基因相关的假基因。跨越Hum1、Hum2和Hum3基因蛋白编码区的cDNA序列分析最终表明，导致NCL的主要缺陷不是3个已知亚基-9基因蛋白编码区的突变。(C)1995 Wiley-Liss，Inc.
The role of subunit-9 of mitochondrial ATP synthase in Batten disease was defined by characterizing the expression of genes encoding this protein in human tissues. Two genetically distinct neuronal ceroid-lipofuscinoses (NCL) comprise Batten disease: the late-infantile (LINCL) and juvenile (JNCL) types. We tested cell lines and tissues from both types of patients, along with normal controls. Differences in expression between diseased and normal samples were found for both mRNA and protein. Antibody staining of subunit-9 protein was detected in LINCL and JNCL tissues, and in 6 LINCL and 4 of 5 JNCL fibroblast lines. No immunoreactivity was seen in fibroblasts from obligate carriers, normal controls, and 6 other storage disease controls, with the exception of faint staining in Niemann-Pick, type C cells. There was an appreciable difference in staining pattern in both tissue sections and fibroblasts between LINCL and JNCL. Three subunit-9 transcripts (Hum1, Hum2, and Hum3) were specifically detected in NCL and normal human tissue from heart, liver, brain, muscle, and pancreas. Transcriptional regulation of subunit-9 genes was found to be altered in Batten disease. Pseudogenes related to each of the subunit 9 genes were isolated. Sequence analysis of cDNAs spanning the protein-coding regions of the Hum1, Hum2, and Hum3 genes showed conclusively that the primary defect(s) causing NCL are not mutations in the protein-coding regions of the 3 known subunit-9 genes. (C) 1995 Wiley-Liss, Inc.