Related Experiment Video
Updated: Apr 4, 2026
Establishment of a Mouse Model with Cough Hypersensitivity via Inhalation of Citric Acid
Published on: January 10, 2025
Thyroid hormone drives the expression of mouse carbonic anhydrase Car4 in kidney, lung and brain
Milica Vujovic1, Susi Dudazy-Gralla1, Joanna Hård1
1Karolinska Institutet, Department of Cell and Molecular Biology, 17177 Stockholm, Sweden.
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.
Insights
Thyroid hormone receptor α1 (TRα1) signaling regulates carbonic anhydrase 4 in adult brain and lung. Thyroid hormone acutely represses renal carbonic anhydrase 4, identifying it as a novel marker for thyroid hormone action.
Area of Science:
- Endocrinology
- Molecular Biology
- Physiology
Background:
- Thyroid hormone regulates critical organ development and function.
- Molecular mechanisms of thyroid hormone action are not fully understood.
- Limited thyroid hormone target genes identified in key tissues.
Purpose of the Study:
- Investigate the role of thyroid hormone receptor α1 (TRα1) in regulating gene expression.
- Identify novel TRα1 target genes in brain, lung, and kidney.
- Assess the functional impact of altered TRα1 signaling on organ function.
Main Methods:
- Utilized a mouse model with a mutation in TRα1.
- Analyzed carbonic anhydrase 4 (CA4) expression in brain, lung, and kidney.
- Measured respiration rate, oxygen saturation, and urine pH.
Main Results:
- TRα1 signaling is essential for adult CA4 expression in lung and brain.
- Thyroid hormone acutely represses renal CA4 mRNA and protein.
- No significant changes in lung function or urine pH observed, suggesting compensatory mechanisms.
Conclusions:
- Identified CA4 as a novel marker of TRα1 action in the brain and lung.
- CA4 serves as a new, negatively regulated target gene for assessing renal thyroid hormone status.
- Other carbonic anhydrases likely compensate for altered CA4 levels, maintaining physiological homeostasis.
Related Concept Videos
00:51Synthesis and Functions of Calcitonin
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
01:18Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...