Deficiency of Globin Messenger RNA in Reticulocytes of the Belgrade Rat

The anemia of the Belgrade laboratory rat, an autosomal recessive trait (b/b), is associated with diminished incorporation of iron into heme and amino acids into globin by reticulocytes. We have studied the basis of decreased globin synthesis in b/b animals. Stimulation of protein synthesis per total RNA by b/b RNA was 39-46% of that by normal RNA in the wheat germ cell-free system. Hybridization of total cytoplasmic RNA to radioactive DNA complementary to rat globin mRNA showed that the number of globin mRNA molecules per total RNA in b/b reticulocytes was about 45% of that in normal reticulocytes. RNA fractions were also characterized by an analysis of globin products on carboxymethylcellulose chromatography after translation of RNA in the wheat germ cell-free system. The globin chain patterns synthesized by total cytoplasmic RNA and polysomal RNA isolated from b/b reticulocytes were indistinguishable from those of normal reticulocytes. The globin patterns synthesized by poly(A)-containing RNA derived from either total cellular or polysomal RNA were also similar when b/b and normal animals were compared. Our results indicate that diminished globin synthesis in b/b animals reflects lowered globin mRNA content in b/b reticulocytes, although the functional composition of globin mRNA from normal and b/b animals is essentially the same. The Belgrade anemia probably results from defective uptake of iron in erythroid cells, leading to heme deficiency; it is attractive to speculate that a chronic heme deficit, in turn, leads to a shortage of globin mRNA.