Aey2, a new mutation in the βB2-crystallin-encoding gene of the mouse

J. Graw, J. Löster, D. Soewarto, H. Fuchs, A. Reis, E. Wolf, R. Balling, M. Hrabé de Angelis

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Purpose. During an ethylnitrosourea (ENU) mutagenesis screen, mice were tested for the occurrence of dominant cataracts. One particular mutant was found that caused progressive opacity and was referred to as Aey2. The purpose of the study was to provide a morphologic description, to map the mutant gene, and to characterize the underlying molecular lesion. Methods. Isolated lenses were photographed, and histologic sections of the eye were analyzed according to standard procedures. Linkage analysis was performed using a set of microsatellite markers covering all autosomal chromosomes. cDNA from candidate genes was amplified after reverse transcription of lens mRNA. Results. The cortical opacification visible at eye opening progressed to an anterior suture cataract and reached its final phenotype as total opacity at 8 weeks of age. There was no obvious difference between heterozygous and homozygous mutants. The mutation was mapped to chromosome 5 proximal to the marker D5Mit138 (8.7 ± 4.2 centimorgan [cM]) and distal to D5Mit15 (12.8 ± 5.4 cM). No recombinations were observed to the markers D5Mit10 and D5Mit25. This position makes the genes within the βA4/βB-crystallin gene cluster excellent candidate genes. Sequence analysis revealed a mutation of T→A at position 553 in the Crybb2 gene, leading to an exchange of Val for Glu. It affects the same region of the Crybb2 gene as in the Philly mouse. Correspondingly, the loss of the fourth Greek key motif is to be expected. Conclusions. The Aey2 mutant represents the second allele of Crybb2 in mice. Because an increasing number of β- and γ-crystallin mutations have been reported, a detailed phenotype-genotype correlation will allow a clearer functional understanding of β- and γ-crystallins.

Original languageEnglish
Pages (from-to)1574-1580
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number7
StatePublished - 2001
Externally publishedYes

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