Casp2-KO Mouse

Casp2, also known as caspase 2, is a gene that plays diverse roles in apoptosis and non-apoptotic processes [3,5]. It is involved in pathways such as the cell cycle, DNA repair, lipid biosynthesis, and regulation of oxidant levels in cells [3]. Additionally, it has been associated with aging, neurodegeneration, and cancer, making it of great biological importance [3]. Genetic models, like knockout (KO) mouse models, can be used to study its functions.

In hepatocellular carcinoma (HCC), Casp2 is related to poor prognosis and worse clinical features. It can reshape the immune microenvironment and influence the response rate of immunotherapy. Drug sensitivity analysis suggests that elevated Casp2 levels may lead to increased susceptibility to doxorubicin and vorinostat, while causing resistance to erlotinib, lapatinib, sunitinib, and temsirolimus. In vitro experiments show that Casp2 can inhibit the proliferation, invasion, and migration ability of HCC cells [1].

In neonatal mice with hypoxic-ischemic brain damage (HIBD), Casp2 is highly expressed. Knockdown of Casp2 alleviates brain injury and cell apoptosis. miR-17-5p targets the 3' UTR of Casp2 and negatively regulates its expression, and overexpression of Casp2 blocks the protective effects of miR-17-5p on HIBD [2].

In autophagy regulation, knockout or knockdown of Casp2 in various cell types and tissues upregulates autophagy, indicating that Casp2 is an endogenous repressor of autophagy [3]. In esophageal adenocarcinoma, CCN1 upregulates Casp2 transcription but suppresses its translation, thus Casp2 does not contribute to CCN1-induced apoptosis in these cells [4].

In conclusion, Casp2 has multiple functions in different biological processes and disease conditions. Its role in apoptosis, autophagy, and disease progression, as revealed through model-based research, especially KO mouse models, provides important insights into the mechanisms of aging, neurodegeneration, and cancer. In specific disease areas like HCC and HIBD, the study of Casp2 using these models helps to understand disease pathogenesis and may guide the development of new treatment strategies.

References:

1. Lou, Yichao, Chen, Desheng, Gu, Qi, Zhu, Qi, Sun, Hongcheng. 2024. PANoptosis-related molecule CASP2 affects the immune microenvironment and immunotherapy response of hepatocellular carcinoma. In Heliyon, 10, e27302. doi:10.1016/j.heliyon.2024.e27302. https://pubmed.ncbi.nlm.nih.gov/38509889/

2. Niu, Xiaolin, Jiao, Zhongmiao, Wang, Zhiguo, Zhang, Hui, Xue, Fei. 2022. MiR-17-5p protects neonatal mice from hypoxic-ischemic brain damage by targeting Casp2. In Neuroscience letters, 772, 136475. doi:10.1016/j.neulet.2022.136475. https://pubmed.ncbi.nlm.nih.gov/35085690/

3. Tiwari, Meenakshi, Sharma, Lokendra K, Vanegas, Difernando, Lechleiter, James D, Herman, Brian. . A nonapoptotic role for CASP2/caspase 2: modulation of autophagy. In Autophagy, 10, 1054-70. doi:10.4161/auto.28528. https://pubmed.ncbi.nlm.nih.gov/24879153/

4. Xu, Ruize, Jiang, Zhenyu, Meng, Xianmei, Dang, Tong, Chai, Jianyuan. 2024. Cellular communication network 1 promotes CASP2 mRNA expression but suppresses its protein translation in esophageal adenocarcinoma. In Journal of cell communication and signaling, 18, e12046. doi:10.1002/ccs3.12046. https://pubmed.ncbi.nlm.nih.gov/39524140/

5. Dorstyn, Loretta, Kumar, Sharad. . Caspase-2 protocols. In Methods in molecular biology (Clifton, N.J.), 1133, 71-87. doi:10.1007/978-1-4939-0357-3_4. https://pubmed.ncbi.nlm.nih.gov/24567095/