title: Aey2, a new mutation in the betaB2-crystallin-encoding gene of the mouse.
abstract: OBJECTIVE
  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 betaA4/betaB-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 beta- and gamma-crystallin mutations have been reported, a detailed phenotype-genotype correlation will allow a clearer functional understanding of beta- and gamma-crystallins.
authors.affiliation: . Forschungszentrum für Umwelt und Gesundheit (GSF. Institute of Experimental Genetics, Neuherberg, Germany. graw@gsf.de
authors.forename: J
authors.initials: J
authors.lastname: Graw
authors.forename: J
authors.initials: J
authors.lastname: Löster
authors.forename: D
authors.initials: D
authors.lastname: Soewarto
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
authors.forename: A
authors.initials: A
authors.lastname: Reis
authors.forename: E
authors.initials: E
authors.lastname: Wolf
authors.forename: R
authors.initials: R
authors.lastname: Balling
authors.forename: M
authors.initials: M
authors.lastname: Hrabé de Angelis
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D003459:Crystallins / Q000235:genetics*; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D007908:Lens, Crystalline / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D038206:beta-Crystallin B Chain / Q000031:analogs & derivatives*
chemical_list: D003459:Crystallins; D012333:RNA, Messenger; D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2