Erythroid defects in TRα-/- mice

Thyroid hormone and its cognate receptor (TR) have been implicated in the production of red blood cells. Here, we show mice deficient for TR alpha have compromised fetal and adult erythropoiesis. Erythroid progenitor numbers were significantly reduced in TR alpha(-/-) fetal livers, and transit through the final stages of maturation was impeded. In addition, immortalized TR alpha(-/-) erythroblasts displayed increased apoptosis and reduced capacity for proliferation and differentiation. Adult TR alpha(-/-) mice had lower hematocrit levels, elevated glucocorticoid levels, and an altered stress erythropoiesis response to hemolytic anemia. Most TR alpha(-/-) animals contained markedly altered progenitor numbers in their spleens. Strikingly, 20% of TR alpha(-/-) mice failed to elicit a stress erythropoiesis response and recovered very poorly from hemolytic anemia. We conclude that an underlying erythroid defect exists in TR alpha(-/-) mice, demonstrating the importance of TR alpha to the erythroid compartment.