Chromosomal localization of the loci responsible for dystrophic cardiac calcinosis in DBA/2 mice

Dystrophic cardiac calcinosis (DCC) occurs in certain inbred strains of mic e, including DBA/2 and C3W He, and is generally found as an incidental lesi on in adult animals at necropsy. Preliminary genetic studies into the cause of DCC have been performed in DBA/2 mice and suggest that DCC is inherited as an autosomal recessive trait involving three or four unlinked genes. To investigate the genetics of DCC fur ther, we produced myocardial cell deat h by freeze-thaw injury to induce DCC. Experiments were conducted with thre e F1 hybrids made using; three inbred strains of mice (DBA/2J and C3H/HeJ, DCC susceptible strains; C57BL/6J, DCC-resistant strain) to compare the gen etic factors in the development of DCC. We found that DBA/2 and C3H/He mice share the same gene pattern(s) that is responsible for DCC. We determined by backcross linkage analysis in DBA/2 and C57BL/6 mice that at least one r ecessive locus is responsible for DCC. A haplotype analysis of the backcros s data demonstrated that the recessive locus, designated dyscalc1, is locat ed on Chromosome 7, 20.5 cM distal to the centromere. The likely candidate genes for dyscalc1 are discussed. Further understanding of the structure an d function of these mutant genes will be beneficial in explaining the molec ular pathogenesis of DCC. (C) 1999 Academic Press.