内源性逆转录病毒插入小鼠No3白内障突变体的Cryge基因中。
Endogenous retroviral insertion in Cryge in the mouse No3 cataract mutant.
作者信息
Nag Nabanita, Peterson Katherine, Wyatt Keith, Hess Sonja, Ray Sugata, Favor Jack, Bogani Debora, Lyon Mary, Wistow Graeme
机构信息
Section on Molecular Structure and Functional Genomics, National Eye Institute, National Institutes of Health, Building 7, Room 201 Bethesda, MD 20892, USA.
出版信息
Genomics. 2007 Apr;89(4):512-20. doi: 10.1016/j.ygeno.2006.12.003. Epub 2007 Jan 12.
No3 (nuclear opacity 3) is a novel congenital nuclear cataract in mice. Microsatellite mapping placed the No3 locus on chromosome 1 between D1Mit480 (32cM) and D1Mit7 (41cM), a region containing seven crystallin genes; Cryba2 and the Cryga-Crygf cluster. Although polymorphic variants were observed, no candidate mutations were found for six of the genes. However, DNA walking identified a murine endogenous retrovirus (IAPLTR1: ERVK) insertion in exon 3 of Cryge, disrupting the coding sequence for gammaE-crystallin. Recombinant protein for the mutant gammaE was completely insoluble. The No3 cataract is mild compared with the effects of similar mutations of gammaE. Quantitative RT-PCR showed that gammaE/F mRNA levels are reduced in No3, suggesting that the relatively mild phenotype results from suppression of gammaE levels due to ERVK insertion. However, the severity of cataract is also strain dependent suggesting that genetic background modifiers also play a role in the development of opacity.
No3（核混浊3）是小鼠中的一种新型先天性核性白内障。微卫星定位将No3基因座定位于1号染色体上D1Mit480（32厘摩）和D1Mit7（41厘摩）之间的区域，该区域包含七个晶状体蛋白基因；Cryba2以及Cryga - Crygf基因簇。尽管观察到了多态性变异，但在其中六个基因中未发现候选突变。然而，DNA步移法在Cryge的外显子3中鉴定出一个小鼠内源性逆转录病毒（IAPLTR1：ERVK）插入，破坏了γE - 晶状体蛋白的编码序列。突变型γE的重组蛋白完全不溶。与γE类似突变的影响相比，No3白内障较为轻微。定量逆转录 - 聚合酶链反应表明，No3中γE/F mRNA水平降低，这表明相对较轻的表型是由于ERVK插入导致γE水平受到抑制所致。然而，白内障的严重程度也具有品系依赖性，这表明遗传背景修饰因子在混浊的发展中也起作用。
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