| First Author | Xia CH | Year | 2006 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 47 |
| Issue | 7 | Pages | 3004-10 |
| PubMed ID | 16799046 | Mgi Jnum | J:112248 |
| Mgi Id | MGI:3655912 | Doi | 10.1167/iovs.06-0178 |
| Citation | Xia CH, et al. (2006) Arginine 54 and Tyrosine 118 residues of {alpha}A-crystallin are crucial for lens formation and transparency. Invest Ophthalmol Vis Sci 47(7):3004-10 |
| abstractText | 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. |
