INVOLVEMENT OF THE TYROSINASE GENE IN THE DEPOSITION OF CARDIAC LIPOFUSCIN IN MICE - ASSOCIATION WITH AORTIC FATTY STREAK DEVELOPMENT

Lipofuscin pigment, a terminal oxidation product, accumulates within c ells during the normal aging process and under certain pathological co nditions. We have analyzed a genetic cross between two inbred mouse st rains, BALB/cJ and a subline of C57BL/6J, which differ in lipofuscin d eposition. A comparison of the segregation pattern of cardiac lipofusc in with the albino locus (c) on mouse chromosome 7 revealed complete c oncordance. Analysis of spontaneous mutants of the tyrosinase gene, en coded by the albino locus, confirmed that the tyrosinase gene itself c ontrols lipofuscin formation. Genetic analysis of other strains indica ted that one or more additional genes can contribute to the inheritanc e of lipofuscin. We also present evidence for an association between c ardiac lipofuscin deposition and aortic fatty streak development in th e mouse.