Ncoa7-KO Mouse

Ncoa7, known as nuclear receptor coactivator 7, is a protein-coding gene. It plays crucial roles in multiple biological processes. Ncoa7 is associated with the regulation of the vacuolar (V)-ATPase, an important proton pump, and is involved in pathways related to endolysosomal homeostasis, which is essential for normal cell function, especially in the nervous system and kidney [2,4]. It also has implications in immune regulation, particularly in inhibiting virus entry [3,5].

In gene knockout studies, Ncoa7 knockout (KO) mice exhibit incomplete distal renal tubular acidosis. They have a persistently high urine pH, develop hypobicarbonatemia after acid loading, and show reduced abundance of several V-ATPase subunits in the kidney, indicating Ncoa7's importance in kidney function and urine acidification [4]. Neurons lacking Ncoa7 in a mouse model display abnormal development, defective lysosomal formation, and abnormal behavior, highlighting its role in neurodevelopment [2]. In clear cell renal cell carcinoma (ccRCC), Ncoa7 overexpression inhibits cell proliferation, invasion, and metastasis in vivo and in vitro by inhibiting the MAPK/ERK pathway [1].

In summary, Ncoa7 is vital for maintaining normal physiological functions in the nervous system and kidney, as well as playing a role in cancer progression. The KO mouse models have significantly contributed to understanding Ncoa7's role in diseases like distal renal tubular acidosis, neurodevelopmental disorders, and ccRCC [1,2,4].

References:

1. Guo, Jiayu, Ke, Shuai, Chen, Qi, Guo, Jia, Qiu, Tao. 2023. NCOA7 Regulates Growth and Metastasis of Clear Cell Renal Cell Carcinoma via MAPK/ERK Signaling Pathway. In International journal of molecular sciences, 24, . doi:10.3390/ijms241411584. https://pubmed.ncbi.nlm.nih.gov/37511343/

2. Castroflorio, Enrico, den Hoed, Joery, Svistunova, Daria, Davies, Benjamin, Oliver, Peter L. 2020. The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour. In Cellular and molecular life sciences : CMLS, 78, 3503-3524. doi:10.1007/s00018-020-03721-6. https://pubmed.ncbi.nlm.nih.gov/33340069/

3. Khan, Hataf, Winstone, Helena, Jimenez-Guardeño, Jose M, Neil, Stuart J D, Malim, Michael H. 2021. TMPRSS2 promotes SARS-CoV-2 evasion from NCOA7-mediated restriction. In PLoS pathogens, 17, e1009820. doi:10.1371/journal.ppat.1009820. https://pubmed.ncbi.nlm.nih.gov/34807954/

4. Merkulova, Maria, Păunescu, Teodor G, Nair, Anil V, Breton, Sylvie, Brown, Dennis. 2018. Targeted deletion of the Ncoa7 gene results in incomplete distal renal tubular acidosis in mice. In American journal of physiology. Renal physiology, 315, F173-F185. doi:10.1152/ajprenal.00407.2017. https://pubmed.ncbi.nlm.nih.gov/29384414/

5. Doyle, Tomas, Moncorgé, Olivier, Bonaventure, Boris, Goujon, Caroline, Malim, Michael H. 2018. The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry. In Nature microbiology, 3, 1369-1376. doi:10.1038/s41564-018-0273-9. https://pubmed.ncbi.nlm.nih.gov/30478388/