title: Mutations in the founder of the MIP gene family underlie cataract development in the mouse.
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 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.
authors.affiliation: Department of Molecular Genetics, University College London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Shiels
authors.forename: S
authors.initials: S
authors.lastname: Bassnett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020346:Aquaporins; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004251:DNA Transposable Elements / Q000235:genetics; D005136:Eye Proteins / Q000032:analysis / Q000235:genetics*; D018703:Founder Effect; D005799:Genes, Dominant; D007908:Lens, Crystalline / Q000737:chemistry; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009115:Muridae; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D020346:Aquaporins; D004251:DNA Transposable Elements; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C030328:aquaporin 0