Ethylnitrosourea-induced mutation in mice leads to the expression of a novel protein in the eye and to dominant cataracts

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Item Type:	Article
Title:	Ethylnitrosourea-induced mutation in mice leads to the expression of a novel protein in the eye and to dominant cataracts
Creators Name:	Graw, J., Klopp, N., Loester, J., Soewarto, D., Fuchs, H., Becker-Follmann, J., Reis, A., Wolf, E., Balling, R. and de Angelis, M.H.
Abstract:	A novel ENU-induced mutation in the mouse leading to a nuclear and zonular opacity of the eye lens (Aey1) was mapped to chromosome 1 between the markers D1Mit303 and D1Mit332. On the basis of the chromosomal position, the γ-crystallin encoding gene cluster (Cryg) and the βA2-crystallin encoding gene Cryba2 were tested as candidate genes. An A → T mutation destroys the start codon of the Cryge gene in the mutants; this mutation was confirmed by the absence of a restriction site for NcoI in the corresponding genomic fragment of homozygous mutants. The next in-frame start codon is 129 bp downstream; this predicted truncated γE-crystallin consists of 131 amino acids, resulting in a molecular mass of 14 kD. However, another open reading frame was observed just 19 bp downstream of the regular Cryge start codon, resulting in a protein of 119 amino acids and a calculated molecular weight of 13 kD. Western blot analysis using polyclonal antibodies against γ-crystallins or the novel Aey1-specific protein demonstrated the specific expression of the Aey1 protein in the cataractous lenses only; the truncated form of the γEcrystallin could not be detected. Therefore, it is concluded that the novel protein destroys the sensitive cellular structure of the eye lens.
Keywords:	Amino Acid Sequence, Base Sequence, Cataract, Codon, Genetic Crosses, Crystalline Lens, Crystallins, Polyacrylamide Gel Electrophoresis, Eye, Genetic Markers, Genetic Models, Haplotypes, Molecular Sequence Data, Mutagens, Mutation, Nucleic Acid Sequence Homology, Open Reading Frames, Polymerase Chain Reaction, Software, Western Blotting, Animals, Mice
Source:	Genetics
ISSN:	0016-6731
Publisher:	Genetics Society Of America
Volume:	157
Number:	3
Page Range:	1313-1320
Date:	1 January 2001
Official Publication:	http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11238416
PubMed:	View item in PubMed

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