Thyroid hormone drives the expression of mouse carbonic anhydrase Car4 in kidney, lung and brain

• Published in: Molecular and cellular endocrinology 2015-11, Vol.416 (C), p.19-26
• Main Authors: Vujovic, Milica, Dudazy-Gralla, Susi, Hård, Joanna, Solsjö, Peter, Warner, Amy, Vennström, Björn, Mittag, Jens
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Carbonic Anhydrase IV - metabolism; Heterozygote; Hydrogen-Ion Concentration; Kidney - metabolism; Lung - metabolism; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Models, Animal; Mutation; Oxygen saturation; Respiration; Respiratory Rate; Thyroid hormone receptor α1; Thyroid Hormone Receptors alpha - genetics; Thyroid Hormone Receptors alpha - metabolism; Thyroid hormone response element; Triiodothyronine - metabolism; Urine
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2015.08.017

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. •Mice with a mutant TRα1 have permanently reduced Car4 in lung and brain.•Renal Car4 expression is suppressed by T3, providing a novel marker for kidney T3 status.•Mice with a mutant TRα1 have normal respiratory rate, oxygen saturation and urine pH levels.