Effects of dietary copper deficiency on male offspring of heterozygous brindled mice.

Female C57BL mice heterozygous for the brindled gene were mated to normal males and fed on a purified diet low in copper throughout gestation and lactation with (+Cu) or without (-Cu) Cu-supplemented drinking water. Male offspring of two genotypes (control, +/y and brindled, Mobr/y) were compared when 10-12 d old. Brindled mice from dams on the -Cu treatment were smaller and had lower packed cell volumes than brindled mice from dams on the +Cu treatment. The -Cu brindled mice were smaller than their littermate brothers (+/y) but had equivalent biochemical features consistent with severe Cu deficiency. Compared with control mice from dams on the +Cu treatment, caeruloplasmin (EC 1.16.3.1) activity was lower in offspring of all three other groups including Mobr/y mice who were not anaemic. Iron levels were similar in organs and bone marrow from all four groups of offspring. When dietary Cu is limiting in brindled mice a more severe Cu deficiency ensues. Thus, appropriate Cu nutriture is important to the management of Menkes' disease in humans, a genetic analogue of the brindled mouse.