Trpc1-KO Mouse

Trpc1, encoding a non-selective cation channel, is the first mammalian Trp channel cloned [1]. It functions as a key component in pathways controlling Ca(2+) entry in response to cell-surface receptor activation, affecting basic cell functions like proliferation, survival, and cell-type specific functions such as neuronal growth cone chemotropic turning [1]. It is involved in store-operated Ca(2+) entry (SOCE) pathways, and its dysregulation may contribute to various diseases [3,4]. Genetically engineered mice with Trpc1 ablation have been crucial for studying its role [1].

In these mouse models, although they can reach adulthood, they exhibit defects in multiple organs and tissues including the cardiovascular, central nervous, skeletal and muscular, and immune systems [1]. Genetic and functional studies using these models have implicated Trpc1 in diseases such as diabetic nephropathy, Parkinson's disease, Huntington's disease, Duchenne muscular dystrophy, cancer, seizures, and Darier-White skin disease [1]. In colon cancer cells, inhibiting Trpc1 expression with tools like difluoromethylornithine (DFMO) eliminates its contribution to SOCE, abolishing cancer hallmarks [2].

In conclusion, Trpc1 plays essential roles in maintaining normal cell functions and Ca(2+) homeostasis through its involvement in SOCE. Studies on Trpc1-KO mouse models have revealed its significance in various disease conditions, such as neurodegenerative diseases, muscular dystrophy, and cancer, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Nesin, Vasyl, Tsiokas, Leonidas. . TRPC1. In Handbook of experimental pharmacology, 222, 15-51. doi:10.1007/978-3-642-54215-2_2. https://pubmed.ncbi.nlm.nih.gov/24756701/

2. Villalobos, Carlos, Hernández-Morales, Miriam, Gutiérrez, Lucía G, Núñez, Lucía. 2019. TRPC1 and ORAI1 channels in colon cancer. In Cell calcium, 81, 59-66. doi:10.1016/j.ceca.2019.06.003. https://pubmed.ncbi.nlm.nih.gov/31203007/

3. Ambudkar, Indu S, de Souza, Lorena Brito, Ong, Hwei Ling. 2016. TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces. In Cell calcium, 63, 33-39. doi:10.1016/j.ceca.2016.12.009. https://pubmed.ncbi.nlm.nih.gov/28089266/

4. Elzamzamy, Osama M, Penner, Reinhold, Hazlehurst, Lori A. 2020. The Role of TRPC1 in Modulating Cancer Progression. In Cells, 9, . doi:10.3390/cells9020388. https://pubmed.ncbi.nlm.nih.gov/32046188/