title: Erythroid defects in TRalpha-/- mice.
abstract: Thyroid hormone and its cognate receptor (TR) have been implicated in the production of red blood cells. Here, we show mice deficient for TRalpha have compromised fetal and adult erythropoiesis. Erythroid progenitor numbers were significantly reduced in TRalpha(-/-) fetal livers, and transit through the final stages of maturation was impeded. In addition, immortalized TRalpha(-/-) erythroblasts displayed increased apoptosis and reduced capacity for proliferation and differentiation. Adult TRalpha(-/-) mice had lower hematocrit levels, elevated glucocorticoid levels, and an altered stress erythropoiesis response to hemolytic anemia. Most TRalpha(-/-) animals contained markedly altered progenitor numbers in their spleens. Strikingly, 20% of TRalpha(-/-) mice failed to elicit a stress erythropoiesis response and recovered very poorly from hemolytic anemia. We conclude that an underlying erythroid defect exists in TRalpha(-/-) mice, demon-strating the importance of TRalpha to the erythroid compartment.
authors.affiliation: Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia.
authors.forename: Tulene S
authors.initials: TS
authors.lastname: Kendrick
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Payne
authors.forename: Michael R
authors.initials: MR
authors.lastname: Epis
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Schneider
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Leedman
authors.forename: S Peter
authors.initials: SP
authors.lastname: Klinken
authors.forename: Evan
authors.initials: E
authors.lastname: Ingley
mesh_terms: D000818:Animals; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D051379:Mice; D018345:Mice, Knockout; D037021:Thyroid Hormone Receptors alpha / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
chemical_list: D037021:Thyroid Hormone Receptors alpha