| Sumario: | Hypothyroidism is often associated with anemia and immunological disorders. Similar defects are found in patients and in mice with a mutated dominant-negative thyroid hormone receptor ¿ (TR¿) and in knockout mice devoid of this receptor, suggesting that this isoform is responsible for the effects of the thyroid hormones in hematopoiesis. However, the hematological phenotype of mice lacking also TR¿ has not yet been examined. We show here that TR¿1/TR¿-knockout female mice, lacking all known thyroid hormone receptors with capacity to bind thyroid hormones, do not have overt anemia and in contrast with hypothyroid mice do not present reduced Gata1 or Hif1 gene expression. Similar to that found in hypothyroidism or TR¿ deficiency during the juvenile period, the B-cell population is reduced in the spleen and bone marrow of ageing TR¿1/TR¿-knockout mice, suggesting that TR¿ does not play a major role in B-cell development. However, splenic hypotrophy is more marked in hypothyroid mice than in TR¿1/TR¿-knockout mice and the splenic population of T-lymphocytes is not significantly impaired in these mice in contrast with the reduction found in hypothyroidism. Our results show that the overall hematopoietic phenotype of the TR¿1/TR¿-knockout mice is milder than that found in the absence of hormone. Although other mechanism/s cannot be ruled out, our results suggest that the unoccupied TRs could have a negative effect on hematopoiesis, likely secondary to repression of hematopoietic gene expression.
|
|---|
