title: Crystallin {gamma}B-I4F mutant protein binds to {alpha}-crystallin and affects lens transparency.
abstract: A new mouse mutant line, Clapper, identified from N-ethyl-N-nitrosurea (ENU)-mutagenized mice, develops a dominant lamellar cataract. The cataract blocks the image of retinal fundus and transmits a fuzzy fluorescein image of retinal vasculature during angiography. The cataractous lens opacity decreases as the mice age. The Clapper mutation has been identified to be a missense mutation of the gammaB-crystallin gene that replaces the 4th isoleucine residue with a phenylalanine (gammaB-I4F). Unlike wild type gammaB, the gammaB-I4F mutant protein binds to alpha-crystallin to form high molecular weight complexes in vivo and in vitro. Circular dichroism measurements indicate that gammaB-I4F protein is less stable than wild type gammaB at high temperature. Darkly stained aggregates, enlarged interfiber spaces, and disorganized and smaller inner mature fibers were found in the regions of the cataract in homozygous Clapper mutant lenses. Thus, the lamellar cataract is likely due to the light-scattering effects of the enlarged interfiber spaces and protein aggregates caused by gammaB-I4F mutant proteins interacting with alpha-crystallin in the lens.
authors.affiliation: School of Optometry and Vision Science Program, University of California, Berkeley, California 94720, USA.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Qingling
authors.initials: Q
authors.lastname: Huang
authors.forename: Linlin
authors.initials: L
authors.lastname: Ding
authors.forename: Hayes W
authors.initials: HW
authors.lastname: McDonald
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.forename: Joseph
authors.initials: J
authors.lastname: Horwitz
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gong
mesh_terms: D000792:Angiography / Q000379:methods; D000818:Animals; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005038:Ethylnitrosourea; D019793:Fluorescein / Q000494:pharmacology; D008040:Genetic Linkage; D006720:Homozygote; D007150:Immunohistochemistry; D007532:Isoleucine / Q000737:chemistry; D007908:Lens, Crystalline / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D009153:Mutagens; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D012171:Retinal Vessels / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014466:Ultraviolet Rays; D038201:alpha-Crystallins / Q000235:genetics; D038222:gamma-Crystallins
chemical_list: D003459:Crystallins; D017931:DNA Primers; D009153:Mutagens; D011994:Recombinant Proteins; D038201:alpha-Crystallins; C107738:crystallin, gammaB; D038222:gamma-Crystallins; D007532:Isoleucine; D010649:Phenylalanine; D005038:Ethylnitrosourea; D019793:Fluorescein