DEFINITION OF THE LOCUS RESPONSIBLE FOR SYSTEMIC CARNITINE DEFICIENCYWITHIN A 1.6-CM REGION OF MOUSE CHROMOSOME-11 BY DETAILED LINKAGE ANALYSIS

Carnitine is an essential cofactor for oxidation of mitochondrial fatt y acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage m yopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mou se, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele map ped to mouse chromosome 11. As a step toward identifying the gene resp onsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (de fined by markers D11Mit24, D11Mit111, D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38, Our resul ts implied that the jvs gene can be sought on mouse chromosome 11 with in a genetic distance no greater than about 1.6 cM. (C) 1996 Academic Press, Inc.