A GUINEA-PIG HEREDITARY CATARACT CONTAINS A SPLICE-SITE DELETION IN A CRYSTALLIN GENE
A GUINEA-PIG HEREDITARY CATARACT CONTAINS A SPLICE-SITE DELETION IN A CRYSTALLIN GENE
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DOI：
10.1016/0925-4439(92)90025-i
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发表时间：
1992-10-13
期刊：
影响因子：
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通讯作者：
BORRAS, T
中科院分区：
文献类型：
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作者：
RODRIGUEZ, IR;GONZALEZ, P;BORRAS, T
豚鼠的先天性白内障为在分子水平上研究遗传性透镜疾病提供了一个独特的机会。zeta-晶体蛋白是最丰富的豚鼠透镜蛋白之一，发现在白内障动物的透镜中发生改变。从白内障透镜文库中分离了几个zeta-晶状体蛋白cDNA克隆，发现其编码区3'端有102-bp缺失。该缺失不干扰阅读框，但导致蛋白质短34个氨基酸。正常基因组zeta-晶体蛋白克隆的序列分析显示，缺失的102 bp片段对应于整个外显子（外显子7）。从白内障动物中分离的基因组DNA的PCR分析表明，外显子7，虽然从mRNA中缺失，但在白内障基因组中是完整的。对zeta-晶状体蛋白基因的进一步序列分析揭示了突变基因内含子6的受体剪接位点处的通用AG的二核苷酸缺失。该突变的存在导致mRNA加工期间外显子7的跳跃，这反过来导致改变的ζ-晶状体蛋白。这是第一次酶/晶体蛋白基因的基因组突变与先天性白内障直接相关。
A congenital cataract present in guinea pigs provided a unique opportunity to study a hereditary lens disease at the molecular level. zeta-Crystallin, one of the most abundant guinea pig lens proteins, was found to be altered in the lens of cataractous animals. Several zeta-crystallin cDNA clones were isolated from a cataractous lens library and found to contain a 102-bp deletion towards the 3' end of the coding region. This deletion does not interfere with the reading frame but results in a protein 34 amino acids shorter. Sequence analysis of a normal genomic zeta-crystallin clone revealed that the missing 102-bp fragment corresponds to an entire exon (exon 7). PCR analysis of the genomic DNA isolated from cataractous animals showed that exon 7, though missing from the mRNA, is intact in the cataractous genome. Further sequence analysis of the zeta-crystallin gene disclosed a dinucleotide deletion of the universal AG at the acceptor splice-site of intron 6 of the mutant gene. The presence of this mutation results in the skipping of exon 7 during the mRNA processing which in turn results in the altered zeta-crystallin protein. This is the first time a genomic mutation in an enzyme/crystallin gene has been directly linked to a congenital cataract.