Genes, manganese, and zinc in formation of otoconia: labeling, recovery, and maternal effects.

Abstract

Published studies indicate that genes and dietary manganese deficiency cause vestibular defects and ataxic behaviors. Manganese deficiency during development causes otoconial defects in mice, rats, guinea pigs, and chicks. Mutant genes cause otoconial defects in mice, mink, and poultry. Manganese supplementation prevents the otoconial defects in some mutant mice and mink. Manganese is essential, before crystallization of the otoconia, for synthesis of mucopolysaccharides and otoconial matrix. Such defects can be induced, after otoconia are crystallized during fetal development, by dietary zinc deficiency and sulfonamide treatment (inhibits carbonic anhydrase, a zinc-requiring enzyme). Manganese and/or zinc supplementation ameliorates otoconial defects in pallid and lethal-milk (zinc-deficient) mice. Studies herein show that: Developing otoconia can be quantitatively labeled with 45 Ca. This may provide a means for studying calcium metabolism in otoconia over a prolonged period of time and for determining the possible effects of diet, drugs, and other factors on otoconia. Otoconial defects, induced after otoconia form in the fetus, were observed in newborn mice, but disappeared by two days after birth. Conditions of the inner ear may contribute to the calcification of otoconia. Manganese and zinc supplementation of pallid mice via acidified drinking water is more effective than dietary supplementation in preventing otoconial defects. The effectiveness of zinc but not of manganese is related to maternal genotype (+/pa vs. pa/pa). The effect of supplementation of the dams with zinc but not with manganese increases over successive litters. These studies indicate the potential for interaction of genes and trace minerals on otoconial formation and maintenance.