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A 76-bp deletion in the Mip gene causes autosomal dominant cataract in Hfi mice. Genomics 2001 Jun 15;74(3):313-9

Date

06/21/2001

Pubmed ID

11414759

DOI

10.1006/geno.2001.6509

Scopus ID

2-s2.0-0035874985 (requires institutional sign-in at Scopus site)   40 Citations

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.

Author List

Sidjanin DJ, Parker-Wilson DM, Neuhäuser-Klaus A, Pretsch W, Favor J, Deen PM, Ohtaka-Maruyama C, Lu Y, Bragin A, Skach WR, Chepelinsky AB, Grimes PA, Stambolian DE

Author

Danielle Sidjanin Maier PhD Nurse Practitioner in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Aquaporins
Blotting, Western
Cataract
Cell Line
Chromosome Mapping
DNA
DNA Mutational Analysis
Eye Proteins
Female
Gene Expression
Genes, Dominant
Genotype
Humans
Lens, Crystalline
Male
Membrane Glycoproteins
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Mutant Strains
Mutation
Oocytes
RNA, Messenger
Sequence Deletion
Xenopus