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First genetically characterized mouse model for age‐related cataracts is a mutation in the bA2‐crystallin encoding gene
Author(s) -
PUK O,
AHMAD N,
WAGNER S,
HRABé DE ANGELIS M,
GRAW J
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.2343.x
Subject(s) - mutant , biology , genetics , crystallin , mutation , gene , candidate gene , cataracts , phenotype , mutagenesis , microbiology and biotechnology
Purpose The purpose of this study was the morphological and genetic characterization of the novel eye‐size mutant Aca30 in the mouse. Methods The eyes of the mutants were investigated by laser interference biometry and histology. Linkage analysis was performed using single nucleotide polymorphisms and micro‐satellite markers. Results Aca30 is a new dominant eye size mutant, which was recovered in an ENU mutagenesis program at the HMGU. The pathologic phenotype is characterized by a clear, but significantly smaller lens. At the age of 11 weeks, the mean lens axis length is 2.1 mm (± 0.01 mm) for wild type mice and 1.9 mm (± 0.03 mm) for heterozygotes. The smaller size of the clear lens was more pronounced in the homozygous mutants (1.7 mm ± 0.03 mm), which were fully fertile and viable. The mutation was mapped to chromosome 1 between the markers D1Mit251 and D1Mit253. Using a positional candidate approach, the bA2‐crastallin encoding gene Cryba2 was sequenced; a T → C exchange at cDNA position 139 leads to an S47P amino acid exchange. Histologically, the eye of newborn homozygous mutants showed small vacuoles at the anterior pole of the lens. At the age of three weeks, some clefts appeared at the anterior cortical region. Later, at the age of 25 weeks, heterozygous lenses developed a subcapsular cortical cataract, while homozygous lenses were completely opaque. Conclusion Our data demonstrate the first mutation in the Cryba2 gene in any organism so far. CRYBA2 should be considered as a candidate for human age‐related cataracts. Moreover, the slightly smaller size of the lens might be understood as an early biomarker for age‐related cataracts.