Cacna1h-KO Mouse

CACNA1H encodes the pore-forming alpha-1H subunit of the voltage-dependent T-type calcium channel CaV3.2. T-type calcium channels are involved in electrical and intracellular calcium oscillations. In the zona glomerulosa of the adrenal cortex, CACNA1H-mediated calcium oscillations govern aldosterone production, which is crucial for electrolyte homeostasis and blood pressure regulation via the kidneys [1,3,4,5].

In mouse models, Cacna1h mutants exhibit tracheal stenosis, disorganized tracheal smooth muscle (SM), and compromised tracheal contraction. CACNA1H is essential for maintaining actin polymerization, required for tracheal SM organization and tube formation, partially mediated through RhoA activation. In human tracheal tissues, decreased CACNA1H protein levels are associated with congenital tracheostenosis [2]. In glioma cells, knockdown of CACNA1H in U251 cells inhibits cell viability, enhances apoptosis, and activates endoplasmic reticulum stress [6].

In conclusion, CACNA1H plays a vital role in multiple biological processes. In the adrenal gland, it is involved in aldosterone production related to blood pressure regulation. In tracheal development, it is essential for SM cytoskeletal organization. In glioma, it acts as an oncogenic gene. Studies on Cacna1h knockout or knockdown models have provided insights into its functions in these biological processes and associated diseases.

References:

1. Dinh, Hoang An, Stölting, Gabriel, Scholl, Ute I. . CaV3.2 (CACNA1H) in Primary Aldosteronism. In Handbook of experimental pharmacology, 279, 249-262. doi:10.1007/164_2023_660. https://pubmed.ncbi.nlm.nih.gov/37311830/

2. Liu, Ziying, Lu, Chunyan, Ma, Li, Stainier, Didier Y R, Yin, Wenguang. 2024. The T-Type Calcium Channel CACNA1H is Required for Smooth Muscle Cytoskeletal Organization During Tracheal Tubulogenesis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2308622. doi:10.1002/advs.202308622. https://pubmed.ncbi.nlm.nih.gov/39360593/

3. Nanba, Kazutaka, Blinder, Amy R, Rege, Juilee, Giordano, Thomas J, Rainey, William E. 2020. Somatic CACNA1H Mutation As a Cause of Aldosterone-Producing Adenoma. In Hypertension (Dallas, Tex. : 1979), 75, 645-649. doi:10.1161/HYPERTENSIONAHA.119.14349. https://pubmed.ncbi.nlm.nih.gov/31983310/

4. Scholl, Ute I. 2022. Genetics of Primary Aldosteronism. In Hypertension (Dallas, Tex. : 1979), 79, 887-897. doi:10.1161/HYPERTENSIONAHA.121.16498. https://pubmed.ncbi.nlm.nih.gov/35139664/

5. Tseng, Chi-Shin, Peng, Kang-Yung, Wang, Shuo-Meng, Wu, Vin-Cent, Chueh, Jeff S. 2022. A Novel Somatic Mutation of CACNA1H p.V1937M in Unilateral Primary Hyperaldosteronism. In Frontiers in endocrinology, 13, 816476. doi:10.3389/fendo.2022.816476. https://pubmed.ncbi.nlm.nih.gov/35757409/

6. Liu, Sheng, Ba, Ying, Li, Chenglong, Xu, Guangming. 2023. Inactivation of CACNA1H induces cell apoptosis by initiating endoplasmic reticulum stress in glioma. In Translational neuroscience, 14, 20220285. doi:10.1515/tnsci-2022-0285. https://pubmed.ncbi.nlm.nih.gov/37250140/