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Mutations in the founder of the MIP gene family underlie cataract development in the mouse

Nature Genetics volume 12, pages 212–215 (1996)Cite this article

Abstract

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 duplication1. Several members of the MIP family transport water (aquaporins), glycerol and other small molecules in microbial, plant and animal cells2. Mutations in two aquaporin homologues of MIP underlie an autosomal recessive form of nephrogenic diabetes insipidus3 and absence of the Colton blood group antigens4 in humans, whereas, mutation of a third MIP-like gene underlies ‘big brain’ development in Drosophila5. 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.

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Author notes

  1. Steven Bassnett

    Present address: Department Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110, USA

Authors and Affiliations

  1. Department of Molecular Genetics, Institute of Ophthalmology, University College London, 11–43 Bath Street, London, EC1V 9EL, UK

    Alan Shiels

  2. Department of Anatomy and Cell Biology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland, 20814, USA

    Steven Bassnett

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Shiels, A., Bassnett, S. Mutations in the founder of the MIP gene family underlie cataract development in the mouse. Nat Genet 12, 212–215 (1996). https://doi.org/10.1038/ng0296-212

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