title: A 76-bp deletion in the Mip gene causes autosomal dominant cataract in Hfi mice.
abstract: Hfi is a dominant cataract mutation where heterozygotes show hydropic lens fibers and homozygotes show total lens opacity. The Hfi locus was mapped to the distal part of mouse chromosome 10 close to the major intrinsic protein (Mip), which is expressed only in cell membranes of lens fibers. Molecular analysis of Mip revealed a 76-bp deletion that resulted in exon 2 skipping in Mip mRNA. In Hfi/Hfi this deletion resulted in a complete absence of the wildtype Mip. In contrast, Hfi/+ animals had the same amount of wildtype Mip as +/+. Results from pulse-chase expression studies excluded hetero-oligomerization of wildtype and mutant Mip as a possible mechanism for cataract formation in the Hfi/+. We propose that the cataract phenotype in the Hfi heterozygote mutant is due to a detrimental gain of function by the mutant Mip resulting in either cytotoxicity or disruption in processing of other proteins important for the lens. Cataract formation in the Hfi/Hfi mouse is probably a combined result of both the complete loss of wildtype Mip and a gain of function of the mutant Mip.
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: D J
authors: DJ
authors: Sidjanin
authors: D M
authors: DM
authors: Parker-Wilson
authors: A
authors: A
authors: Neuhäuser-Klaus
authors: W
authors: W
authors: Pretsch
authors: J
authors: J
authors: Favor
authors: P M
authors: PM
authors: Deen
authors: C
authors: C
authors: Ohtaka-Maruyama
authors: Y
authors: Y
authors: Lu
authors: A
authors: A
authors: Bragin
authors: W R
authors: WR
authors: Skach
authors: A B
authors: AB
authors: Chepelinsky
authors: P A
authors: PA
authors: Grimes
authors: D E
authors: DE
authors: Stambolian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020346:Aquaporins; D015153:Blotting, Western; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D002874:Chromosome Mapping; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014981:Xenopus
chemical_list: D020346:Aquaporins; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C030328:aquaporin 0; D004247:DNA