Investigations in Normal Heterozygous and

An auto#{225}omal recessive mutant (symbol, dan) in the dog causes chondrodysplastic dwarfism and mild anemia as pleiotropic effects. The anemia is characterized by stomatocytosis, macrocytosis, low MCHC, increased osmotic fragility, shortened red cell survival, reticulocytosis, erythroid hyperplasia, and increased iron turnover. Minor changes can be detected in the red cells of heterozygous carriers of the dan gene, but red cell survival is normal and chondrodysplasia is not present. Red cell sodium concentration and water content are increased in anemic dogs and to a lesser degree in carriers. Glutathione deficiency is present. The disorder described here resembles a number of human hemolytic anemias with stomatocytosis, glutathione deficiency, and disordered red cell cation and water content, and further study of the dan mutant, together with investigations of the hereditary human conditions, will elucidate the maintenance of normal red cell cation balance.