title: Thyroid hormone drives the expression of mouse carbonic anhydrase Car4 in kidney, lung and brain.
abstract: Thyroid hormone is a well-known regulator of brain, lung and kidney development and function. However, the molecular mechanisms by which the hormone exerts its function have remained largely enigmatic, and only a limited set of target genes have been identified in these tissues. Using a mouse model with a mutation in thyroid hormone receptor α1 (TRα1), we here demonstrate that the expression of carbonic anhydrase 4 in lung and brain of the adult animal depends on intact TRα1 signaling. In the kidney, carbonic anhydrase 4 mRNA and protein are not affected by the mutant TRα1, but are acutely repressed by thyroid hormone. However, neither lung function--as measured by respiration rate and oxygen saturation--nor urine pH levels were affected by altered carbonic anhydrase 4 levels, suggesting that other carbonic anhydrases are likely to compensate. Taken together, our findings identify a previously unknown marker of TRα1 action in brain and lung, and provide a novel negatively regulated target gene to assess renal thyroid hormone status.
authors: Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden.
authors: Milica
authors: M
authors: Vujovic
authors: Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden.
authors: Susi
authors: S
authors: Dudazy-Gralla
authors: Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden.
authors: Joanna
authors: J
authors: Hård
authors: Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden.
authors: Peter
authors: P
authors: Solsjö
authors: Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden.
authors: Amy
authors: A
authors: Warner
authors: Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden.
authors: Björn
authors: B
authors: Vennström
authors: Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden; Universität zu Lübeck, Medizinische Klinik 1/Center of Brain, Behavior and Metabolism, Ratzeburger Allee 160, 23562 Lübeck, Germany. Electronic address: jens.mittag@uni-luebeck.de.
authors: Jens
authors: J
authors: Mittag
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D030741:Carbonic Anhydrase IV / Q000378:metabolism*; D006579:Heterozygote; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009154:Mutation; D056152:Respiratory Rate; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine; D030741:Carbonic Anhydrase IV; C548248:Car4 protein, mouse
keywords: Mutation; Oxygen saturation; Respiration; Thyroid hormone receptor α1; Thyroid hormone response element; Urine; pH