Ninj2, also known as nerve injury-induced protein 2, is involved in multiple biological processes. It is associated with pathways like laminin-integrin signaling, insulin signaling, and IGF1R-related signaling, and is of biological importance in areas such as myelination, adipogenesis, and liver fibrosis. Genetic models, especially knockout (KO) mouse models, have been crucial for studying Ninj2 [1,2,3].

In KO mouse models, Ninj2-deficient mice showed precocious myelination and accelerated remyelination after sciatic nerve injury, indicating Ninj2 negatively regulates Schwann cells development by interfering laminin-integrin signaling [1]. NINJ2-knockout mice also exhibited impaired adipogenesis, increased insulin resistance, and abnormal glucose homeostasis as NINJ2 deficiency inhibits preadipocyte differentiation by blocking insulin-induced mitotic clonal expansion [2]. In liver fibrosis models, global Ninj2 knockout reversed the fibrotic phenotype, while hepatocyte-specific overexpression of Ninj2 exacerbated it. Ninj2 promotes liver fibrosis by interacting with IGF1R and increasing the secretion of PDGF-BB in hepatocytes [3]. Mice with oligodendrocyte-specific deletion of Ninj2 showed depressive-like behaviors due to inhibited oligodendrocyte development and myelination [4].

In conclusion, Ninj2 plays diverse roles in myelination, adipogenesis, insulin sensitivity, liver fibrosis, and the development of depressive-like behaviors. The use of Ninj2 KO/CKO mouse models has significantly contributed to understanding its functions in these disease-related biological processes, providing potential therapeutic targets for conditions such as nerve injury, metabolic disorders, liver fibrosis, and depression.

References:

1. Sun, Yuxia, Chen, Xiang, Yue, Cen, Ou, Zhimin, Chen, Ying. 2022. Ninj2 regulates Schwann cells development by interfering laminin-integrin signaling. In Theranostics, 12, 7307-7318. doi:10.7150/thno.76131. https://pubmed.ncbi.nlm.nih.gov/36438492/

2. Peng, Huixin, Yu, Yubing, Wang, Pengyun, Wang, Qing K, Xu, Chengqi. 2022. NINJ2 deficiency inhibits preadipocyte differentiation and promotes insulin resistance through regulating insulin signaling. In Obesity (Silver Spring, Md.), 31, 123-138. doi:10.1002/oby.23580. https://pubmed.ncbi.nlm.nih.gov/36504350/

3. Wang, Yifan, Wang, Pengyun, Yu, Yubing, Wang, Qing K, Xu, Chengqi. 2022. Hepatocyte Ninjurin2 promotes hepatic stellate cell activation and liver fibrosis through the IGF1R/EGR1/PDGF-BB signaling pathway. In Metabolism: clinical and experimental, 140, 155380. doi:10.1016/j.metabol.2022.155380. https://pubmed.ncbi.nlm.nih.gov/36549436/

4. Sun, Yuxia, Chen, Xiang, Ou, Zhimin, Liu, Changqin, Chen, Ying. 2021. Dysmyelination by Oligodendrocyte-Specific Ablation of Ninj2 Contributes to Depressive-Like Behaviors. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9, e2103065. doi:10.1002/advs.202103065. https://pubmed.ncbi.nlm.nih.gov/34787377/