Nisch-KO Mouse

NISCH, which encodes the imidazoline receptor Nischarin, has tumor-suppressor-like characteristics. It functions as a cytosolic scaffolding protein and is involved in regulating multiple biological activities such as cell migration, metabolic homeostasis, and dendritic spine morphogenesis, and is associated with pathways like the FAK signal pathway [2,3,1,4]. Genetic models are valuable for studying its functions.

A novel NISCHΔ5-6 knockout mouse model showed that Nischarin deletion enhanced cell migration and reduced oxidative metabolism and overall ATP production, with significant changes in the expression of genes related to lipid and fat metabolism and cell growth [3]. In vivo, overexpression of NISCH in mice led to impaired spatial working memory, and drugs targeting Nischarin could rescue this impairment [1]. In ovarian cancer, NISCH knockdown via promoter hypermethylation promoted tumor proliferation and invasion by affecting cell-cycle progression and the FAK signal pathway [4].

In conclusion, NISCH plays essential roles in cell metabolism, migration, and cognitive function. Studies using knockout mouse models have revealed its significance in metabolic homeostasis and in diseases such as ovarian cancer and psychiatric disorders, providing insights into potential therapeutic targets.

References:

1. Yang, Zhi-Hui, Cai, Xin, Ding, Zhong-Li, Chang, Hong, Xiao, Xiao. 2023. Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function. In BMC medicine, 21, 254. doi:10.1186/s12916-023-02931-6. https://pubmed.ncbi.nlm.nih.gov/37443018/

2. Okpechi, Samuel C, Yousefi, Hassan, Nguyen, Khoa, Burow, Matthew E, Alahari, Suresh K. 2022. Role of Nischarin in the pathology of diseases: a special emphasis on breast cancer. In Oncogene, 41, 1079-1086. doi:10.1038/s41388-021-02150-4. https://pubmed.ncbi.nlm.nih.gov/35064214/

3. Nguyen, Tina H, Yousefi, Hassan, Okpechi, Samuel C, Yang, Qinglin, Alahari, Suresh K. 2022. Nischarin Deletion Reduces Oxidative Metabolism and Overall ATP: A Study Using a Novel NISCHΔ5-6 Knockout Mouse Model. In International journal of molecular sciences, 23, . doi:10.3390/ijms23031374. https://pubmed.ncbi.nlm.nih.gov/35163298/

4. Li, Jing, He, Xiaoying, Dong, Ruofan, Yu, Jinjin, Qiu, Haifeng. 2015. Frequent Loss of NISCH Promotes Tumor Proliferation and Invasion in Ovarian Cancer via Inhibiting the FAK Signal Pathway. In Molecular cancer therapeutics, 14, 1202-12. doi:10.1158/1535-7163.MCT-14-0911. https://pubmed.ncbi.nlm.nih.gov/25724667/