Celf2-KO Mouse

CELF2, also known as CUGBP ELAV-like family number 2, is an RNA-binding protein. It plays a crucial role in regulating RNA splicing, and is involved in various biological processes. It has been associated with pathways such as the PI3-K/Akt signaling pathway, and is of great biological importance in normal development and disease [2]. Genetic models, like knockout (KO) mouse models, are valuable tools for studying its functions.

In KO mouse models, Celf2 deficiency in the hematopoietic system enhanced HSCs self-renewal and myeloid cell differentiation, accelerating myeloid cell transformation and AML development through the FAT10-mTORC1 axis [1]. In the nervous system, Celf2 Nestin-Cre heterozygous knockout mice showed autism-like behaviors, with an underdeveloped cerebral cortex, reduced dendritic spine density, and affected synaptic maturation [4]. In cancer, overexpression of CELF2 in non-small cell lung carcinoma inhibited tumor growth by interfering with the PREX2-PTEN interaction [2]. It also sustained a proliferating/OLIG2+ glioblastoma cell phenotype via epigenetic repression of SOX3, and its deficiency reduced tumor growth in nude mice [3]. In pancreatic cancer, downregulation of CELF2 affected tumorigenesis through regulating CD44 alternative splicing and the ERAD pathway [5].

In conclusion, Celf2 is essential for normal cellular functions, with its deficiency often leading to abnormal biological processes. KO/CKO mouse models have revealed its significant roles in leukemia, autism-related neurodevelopmental disorders, and multiple cancers, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Guo, Tengxiao, Wang, Yuxia, Sun, Xiaolu, Yuan, Weiping, Wang, Xiaomin. 2024. Loss of RNA-binding protein CELF2 promotes acute leukemia development via FAT10-mTORC1. In Oncogene, 43, 1476-1487. doi:10.1038/s41388-024-03006-3. https://pubmed.ncbi.nlm.nih.gov/38514854/

2. Yeung, Yiu To, Fan, Suyu, Lu, Bingbing, Bode, Ann M, Dong, Zigang. . CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction. In Carcinogenesis, 41, 377-389. doi:10.1093/carcin/bgz113. https://pubmed.ncbi.nlm.nih.gov/31241130/

3. Turchi, Laurent, Sakakini, Nathalie, Saviane, Gaelle, Burel-Vandenbos, Fanny, Virolle, Thierry. 2023. CELF2 Sustains a Proliferating/OLIG2+ Glioblastoma Cell Phenotype via the Epigenetic Repression of SOX3. In Cancers, 15, . doi:10.3390/cancers15205038. https://pubmed.ncbi.nlm.nih.gov/37894405/

4. Duan, Xinyu, Peng, Xiaoxia, Jia, Xiangbin, Tan, Jieqiong, Hu, Zhangxue. 2024. CELF2 Deficiency Demonstrates Autism-Like Behaviors and Interferes with Late Development of Cortical Neurons in Mice. In Molecular neurobiology, 62, 156-168. doi:10.1007/s12035-024-04250-0. https://pubmed.ncbi.nlm.nih.gov/38829512/

5. Lai, Shihui, Wang, Yan, Li, Ting, Zhang, Xiang, Lin, Chengjie. 2022. N6-methyladenosine-mediated CELF2 regulates CD44 alternative splicing affecting tumorigenesis via ERAD pathway in pancreatic cancer. In Cell & bioscience, 12, 125. doi:10.1186/s13578-022-00844-0. https://pubmed.ncbi.nlm.nih.gov/35941702/