A LOCUS ON CHROMOSOME-7 DETERMINES MYOCARDIAL-CELL NECROSIS AND CALCIFICATION (DYSTROPHIC CARDIAC CALCINOSIS) IN MICE

Dystrophic cardiac calcinosis, an age-related cardiomyopathy that occu rs among certain inbred strains of mice, involves myocardial injury, n ecrosis, and calcification. Using a complete linkage map approach and quantitative trait locus analysis, we sought to identify genetic loci determining dystrophic cardiac calcinosis in an Fz intercross of resis tant C57BL/6J and susceptible C3H/HeJ inbred strains. We identified a single major locus, designated Dyscalc, located on proximal chromosome 7 in a region syntenic with human chromosomes 19q13 and 11p15. The st atistical significance of Dyscalc (logarithm of odds score 14.6) was t ested by analysis of permuted trait data. Analysis of BxH recombinant inbred strains confirmed the mapping position. The inheritance pattern indicated that this locus influences susceptibility of cells both to enter necrosis and to subsequently undergo calcification.