Itpr2, also known as inositol 1,4,5-trisphosphate receptor, type 2, is an endoplasmic reticulum calcium-release channel. It is involved in calcium fluxes from the ER to the mitochondria and plays a crucial role in calcium homeostasis [1,2]. This function is essential as calcium signaling is fundamental for various cellular processes, such as cell cycle progression, differentiation, and apoptosis.

In Itpr2 knockout (KO) mice, there is improved aging, including increased lifespan, better metabolic stress response, less immunosenescence, and reduced liver steatosis and fibrosis [1]. In OL-specific Itpr2 KO adolescent mice, Ca2+ homeostasis is disturbed, myelination is inhibited, and anxiety/depressive-like behaviors are exhibited [2]. Astrocytic calcium-deficient Itpr2-/-mice display abnormal resting-state functional connectivity in depression-related networks [3].

In conclusion, Itpr2 is essential for regulating cellular senescence, aging, myelination, and emotional behaviors. The Itpr2 KO mouse models have significantly contributed to understanding its role in age-related pathologies, myelin-associated psychiatric disorders, and depression.

References:

1. Ziegler, Dorian V, Vindrieux, David, Goehrig, Delphine, Martin, Nadine, Bernard, David. 2021. Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging. In Nature communications, 12, 720. doi:10.1038/s41467-021-20993-z. https://pubmed.ncbi.nlm.nih.gov/33526781/

2. Zhang, Ming, Zhi, Na, Feng, Jiaxiang, Wu, Shengxi, Zhao, Xianghui. 2024. ITPR2 Mediated Calcium Homeostasis in Oligodendrocytes is Essential for Myelination and Involved in Depressive-Like Behavior in Adolescent Mice. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2306498. doi:10.1002/advs.202306498. https://pubmed.ncbi.nlm.nih.gov/38476116/

3. Liu, Jiaming, Mo, Jia-Wen, Wang, Xunda, Feng, Yanqiu, Cao, Xiong. 2022. Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression. In Science advances, 8, eabo2098. doi:10.1126/sciadv.abo2098. https://pubmed.ncbi.nlm.nih.gov/36383661/