Document Detail

Arginine 54 and Tyrosine 118 residues of {alpha}A-crystallin are crucial for lens formation and transparency.
MedLine Citation:
PMID:  16799046     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To identify new mouse models for studying roles of alphaAlpha-crystallin in vivo and to investigate why and how different mutations of the alphaAlpha-crystallin gene lead to dominant or recessive cataracts. METHODS: Using mouse genetic approaches and slit lamp screening, we identified two mouse cataractous mutant lines. Causative genes were mapped by a genome-wide linkage analysis. DNA sequencing verified missense mutations of alphaA-crystallin gene in both mutant lines. Histology, imaging of green fluorescent protein (GFP)-positive lenses, and protein 2-DE gel were used to determine the morphologic and biochemical properties of mutant lenses. RESULTS: Two new alphaA-crystallin gene mutations were identified, alphaA-R54C (alphaA-Cys) and alphaA-Y118D, which cause recessive whole cataracts and dominant nuclear cataracts, respectively. In homozygous alphaA-Cys mutant mice, lens epithelial and fiber cells lost their characteristic cellular features and developed disrupted subcellular structures, such as actin filaments and mitochondria. The nuclear cataract caused by alphaA-Y118D mutation was associated with increased water-insoluble crystallins (alpha, beta, and gamma classes). These results suggest that the Arg54 residue in the N-terminal region is crucial for alphaA-crystallin to perform its roles in lens epithelial and fiber cells during development, whereas the Y118D mutation in the central alpha-crystallin domain impairs alphaA-crystallin's ability to maintain the solubility of crystallin proteins in the lens. CONCLUSIONS: This work demonstrates that different regions of alphaA-crystallin mediate distinct functions in vivo. These two mutant mouse lines provide useful animal models for further investigating the multiple roles of alphaA-crystallin in the lens.
Chun-hong Xia; Haiquan Liu; Bo Chang; Catherine Cheng; Debra Cheung; Meng Wang; Qingling Huang; Joseph Horwitz; Xiaohua Gong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  47     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-26     Completed Date:  2006-08-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3004-10     Citation Subset:  IM    
School of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, California 94720-2020, USA.
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MeSH Terms
Actins / metabolism
Arginine / physiology*
Cataract / genetics*,  pathology
Chromosome Mapping
Disease Models, Animal
Electrophoresis, Gel, Two-Dimensional
Epithelial Cells / physiology
Genes, Dominant
Genes, Recessive
Green Fluorescent Proteins
Lens, Crystalline / physiology*
Linkage (Genetics)
Mice, Inbred C3H
Mice, Inbred C57BL
Mitochondria / pathology
Point Mutation*
Tyrosine / physiology*
alpha-Crystallin A Chain / genetics*
Grant Support
Reg. No./Substance:
0/Actins; 0/alpha-Crystallin A Chain; 147336-22-9/Green Fluorescent Proteins; 55520-40-6/Tyrosine; 74-79-3/Arginine

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