IMPAIRED COPPER UTILIZATION IN THE COPPER-DEFICIENT BRINDLED MOUSE MUTANT

Abstract

The Brindled mouse mutant is a model for the Kinky Hair syndrome. Male Brindled hemizygous suckling mice demonstrate poor growth and neurologic deterioration beginning during the first week of life and ending with death by the end of the second week. Newborn Brindled carriers are asymptomatic with normal brain copper concentration; liver copper concentration is low and the renal copper is high. Newborn carrier pups suckled by Brindled dams put on low copper diets on the day of parturition, however, show deficient weight gain by the age of 6 days and by 12 days weigh approximately one-half their normal litter-mates. Neurologic symptoms developed in the copper-deficient young carriers by age 12-14 days while their normal litter-mates remained asymptomatic. Tissue copper studies demonstrate that the liver and brain copper concentration in the carrier is no different from that of the normals, although the renal copper is greater than twice as high. On copper-deficient diets, the brain and liver concentrations of normal and heterozygous young decrease to comparable levels, but heterozygotes also develop systemic and neurologic symptoms. These observations are thought to implicate an abnormality in copper utilization in Brindled carriers brought out by marginal copper intake.