Differential synthesis and degradation of protein in the hereditary Philly mouse cataract

Lens protein metabolism was investigated in the Philly mouse between the third and eighth postnatal week. As demonstrated in an accompanying article, the Philly mouse develops a hereditary, osmotic, cataract associated with influx of Na⁺ and loss of K⁺ during this time interval. The contents of β- and γ-crystallin were strikingly reduced in the Philly lens, as judged by sodium dodecyl sulfate (SDS)-urea-polyacrylamide gel electrophoresis and by immunodiffusion. This appeared to be due to proteolysis, since there were negligible amounts of crystallins found in the medium of cultured Philly lenses. α-Crystallin remained in the Philly lens but apparently accumulated discrete polypeptide cleavage products. The incorporation of [³⁵S]methionine into β- and γ-crystallin polypeptides was markedly reduced in the Philly lens. By contrast, the incorporation of [³⁵S]methionine into the α-crystallin and the higher molecular weight non-crystallin polypeptides was as great if not greater, in the Philly lens than in the normal lens. The non-crystallin polypeptides were associated with the 10 000 × g pellet of the homogenate. The present data extend the correlation between alterations in protein metabolism and electrolyte concentrations to this hereditary cataract, and support the idea that selective degradation of crystallins and differential reduction in the synthesis of crystallins are primary causes for the lowered amounts of soluble protein—especially β- and γ-crystallin—found in cataracts associated with ionic imbalances.