New Dyscalc loci for myocardial cell necrosis and calcification (dystrophic cardiac calcinosis) in mice

Dystrophic cardiac calcinosis (DCC) occurs among certain inbred strains of mice and involves necrosis and subsequent calcification as response of myoc ardial tissue to injury. Using a complete linkage map approach, we investig ated the genetics of DCC in an F-2 intercross of resistant C57BL/6J and sus ceptible C3H/HeJ inbred strains and identified previously a major predispos ing quantitative trait locus (QTL), Dyscalc1, on proximal chromosome 7. Ana lysis of inheritance suggested, however, that DCC is influenced by addition al modifier QTL, which have as yet not been mapped. Here, we report the ide ntification by composite interval mapping of the DCC loci Dyscalc2, Dyscalc 3, and Dyscalc4 on chromosomes 4, 12 and 14, respectively. Together, the fo ur Dyscalc loci explained 47% of the phenotypic variance of DCC, which was induced by a high-fat diet. Additive epistasis between Dyscalc1 and Dyscalc 2 enhanced DCC. Examining recombinant inbred strains, we propose a 10-cM in terval containing Dyscalc1 and discuss potential candidate genes.