Identification of proteins that modify cataract of mouse eye lens.
The occurrence of a nuclear cataract in the eye lens due to disruption of the alpha3Cx46 connexin gene, Gja3, is dependent on strain background in a mouse model, implicating factors that modify the pathology. The differences upon cataractogenesis in the urea soluble proteins of the lens of two mouse strains, C57BL/6J and 129/SvJ, were analyzed by a comparative proteomics approach. Determination of the complete proteome of an organ offers the opportunity to characterize at a molecular level, differences in gene expression and PTMs occurring during pathology and between individuals. The abundance of 63 protein species was altered between the strains. A unique aspect of this study is the identification of chaperonin subunit 6A, mortalin, ERp29, and syntaxin-binding protein 6 in the eye lens. DNA polymorphisms resulting in nonconservative amino acid changes that led to altered physicochemical properties of the proteins were detected for mortalin, chaperonin subunit 6A, annexin A1, and possibly gamma-N crystallin. The results show HSP27/25 and/or ERp29 are the likely major modifying factors for cataractogenesis. Extension of the results suggests that small heat-shock proteins have a major role for influencing cataract formation in humans.
Hoehenwarter
Wolfgang
W
Max Planck Institute for Infection Biology, Core Facility Protein Analysis, Berlin, Germany.
Tang
Yajun
Y
Ackermann
Renate
R
Pleissner
Klaus-Peter
KP
Schmid
Monika
M
Stein
Robert
R
Zimny-Arndt
Ursula
U
Kumar
Nalin M
NM
Jungblut
Peter R
PR
D000818:Animals; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D003459:Crystallins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005136:Eye Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007908:Lens, Crystalline / Q000737:chemistry* / Q000473:pathology*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003459:Crystallins; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D018832:Molecular Chaperones; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C084808:phakinin