Atp2b3-KO Mouse

Atp2b3, also known as plasma membrane Ca2+ transporting ATPase 3, is crucial for calcium transportation. It is involved in multiple biological processes, and its dysregulation is associated with various diseases. Mutations in Atp2b3 can disrupt normal ion transportation, cell membrane potential, and aldosterone production, highlighting its importance in physiological regulation [2,4,5,6,7].

In HT-22 cells, knockdown of Atp2b3 alleviated erastin-induced ferroptosis. It reversed the changes in cell viability, ROS levels, and the expression of oxidative stress-related proteins in the P62-KEAP1-NRF2-HO-1 pathway [1]. In primary aldosteronism, somatic mutations in Atp2b3 have been identified in aldosterone-producing adenomas. These mutations, such as the novel ATP2B3 K416_F418delinsN and c.1269_1274delTGTGCT, increase CYP11B2 expression and aldosterone production [3,6].

In conclusion, Atp2b3 is essential for calcium-related physiological functions. Its role in ferroptosis and primary aldosteronism, as revealed through functional studies including gene knockdown in cell models, provides insights into the pathogenesis of related diseases. Understanding Atp2b3's functions can potentially contribute to developing new therapeutic strategies for neurological disorders and primary aldosteronism.

References:

1. Guo, Shihui, Zhong, Aiying, Zhang, Dongxu, Zhao, Ruqian, Ma, Wenqiang. 2023. ATP2B3 Inhibition Alleviates Erastin-Induced Ferroptosis in HT-22 Cells through the P62-KEAP1-NRF2-HO-1 Pathway. In International journal of molecular sciences, 24, . doi:10.3390/ijms24119199. https://pubmed.ncbi.nlm.nih.gov/37298147/

2. 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/

3. Liao, Hung-Wei, Peng, Kang-Yung, Wu, Vin-Cent, Lin, Wei-Chou, Chueh, Jeff S. 2021. Characteristics of a Novel ATP2B3 K416_F418delinsN Mutation in a Classical Aldosterone-Producing Adenoma. In Cancers, 13, . doi:10.3390/cancers13184729. https://pubmed.ncbi.nlm.nih.gov/34572956/

4. Pitsava, Georgia, Faucz, Fabio R, Stratakis, Constantine A, Hannah-Shmouni, Fady. 2022. Update on the Genetics of Primary Aldosteronism and Aldosterone-Producing Adenomas. In Current cardiology reports, 24, 1189-1195. doi:10.1007/s11886-022-01735-z. https://pubmed.ncbi.nlm.nih.gov/35841527/

5. Williams, Tracy Ann, Monticone, Silvia, Schack, Vivien R, Vilsen, Bente, Mulatero, Paolo. 2013. Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas. In Hypertension (Dallas, Tex. : 1979), 63, 188-95. doi:10.1161/HYPERTENSIONAHA.113.01733. https://pubmed.ncbi.nlm.nih.gov/24082052/

6. Murakami, Masanori, Yoshimoto, Takanobu, Minami, Isao, Kihara, Kazunori, Ogawa, Yoshihiro. . A Novel Somatic Deletion Mutation of ATP2B3 in Aldosterone-Producing Adenoma. In Endocrine pathology, 26, 328-33. doi:10.1007/s12022-015-9400-9. https://pubmed.ncbi.nlm.nih.gov/26481629/

7. Jouinot, Anne, Armignacco, Roberta, Assié, Guillaume. 2019. Genomics of benign adrenocortical tumors. In The Journal of steroid biochemistry and molecular biology, 193, 105414. doi:10.1016/j.jsbmb.2019.105414. https://pubmed.ncbi.nlm.nih.gov/31207362/