Shiels A, Bassnett S
Department of Molecular Genetics, University College London, UK.
Nat Genet. 1996 Feb;12(2):212-5. doi: 10.1038/ng0296-212.
The major intrinsic protein (MIP) of the vertebrate eye lens is the first identified member of a sequence-related family of cell-membrane proteins that appears to have evolved by gene duplication. Several members of the MIP family transport water (aquaporins), glycerol and other small molecules in microbial, plant and animal cells. Mutations in two aquaporin homologues of MIP underlie an autosomal recessive form of nephrogenic diabetes insipidus and absence of the Colton blood group antigens in humans, whereas, mutation of a third MIP-like gene underlies 'big brain' development in Drosophila. Here we show that distinct mutations in the murine Mip gene underlie one form of autosomal dominant cataract in the mouse. The cataract Fraser mutation is a transposon-induced splicing error that substitutes a long terminal repeat sequence for the carboxy-terminus of MIP. The lens opacity mutation is an amino-acid substitution that inhibits targeting of MIP to the cell-membrane. These allelic cataract mutations provide the first direct evidence that MIP plays a crucial role in the development of a transparent eye lens.
脊椎动物眼晶状体的主要内在蛋白（MIP）是细胞相关膜蛋白序列家族中首个被鉴定的成员，该家族似乎是通过基因复制进化而来。MIP家族的几个成员在微生物、植物和动物细胞中负责运输水（水通道蛋白）、甘油及其他小分子。人类中，MIP的两种水通道蛋白同源物发生突变会导致常染色体隐性遗传性肾源性尿崩症以及科尔顿血型抗原缺失；而果蝇中，第三个类MIP基因的突变是“大脑袋”发育的原因。在此，我们表明，小鼠Mip基因的不同突变是小鼠常染色体显性白内障的一种形式的病因。白内障弗雷泽突变是一种转座子诱导的剪接错误，它用一个长末端重复序列替代了MIP的羧基末端。晶状体混浊突变是一种氨基酸替代，它会抑制MIP靶向细胞膜。这些等位基因性白内障突变首次直接证明了MIP在透明眼晶状体发育中起着关键作用。
