Rag1, the recombination activating gene 1, is crucial for V(D)J recombination in developing T and B lymphocytes, which is essential for generating diverse antigen receptors and thus for a functional adaptive immune system [3,4,5,6]. This process is integral to the proper development and function of the immune system.

Rag1 -/- mice, a gene knockout model, have been used to study its role. In these mice, the lack of functional lymphocytes due to Rag1 deficiency results in reduced perfusion recovery and impaired arteriogenesis, with reduced vascular cell proliferation, a smaller inner luminal diameter, and a shift in perivascular macrophage polarization to a more pro-inflammatory M1-like state [2]. Also, gene editing strategies targeting the human Rag1 gene in hematopoietic stem and progenitor cells (HSPCs) have been developed. In-frame insertion into exon 2 of Rag1 can drive physiologic human Rag1 expression and activity, potentially overcoming T and B cell differentiation blocks in patients with hypomorphic Rag1 mutations [1].

In conclusion, Rag1 is essential for V(D)J recombination and proper immune system function. The use of Rag1 knockout mouse models has revealed its role in arteriogenesis, and gene editing studies show potential for treating Rag1-related immunodeficiency. These findings contribute to understanding immune-related diseases and developing new treatment strategies [1,2].

References:

1. Castiello, Maria Carmina, Brandas, Chiara, Ferrari, Samuele, Naldini, Luigi, Villa, Anna. 2024. Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency. In Science translational medicine, 16, eadh8162. doi:10.1126/scitranslmed.adh8162. https://pubmed.ncbi.nlm.nih.gov/38324638/

2. Kumaraswami, Konda, Arnholdt, Christoph, Deindl, Elisabeth, Lasch, Manuel. 2023. Rag1 Deficiency Impairs Arteriogenesis in Mice. In International journal of molecular sciences, 24, . doi:10.3390/ijms241612839. https://pubmed.ncbi.nlm.nih.gov/37629019/

3. Gan, Tingting, Wang, Yuhong, Liu, Yang, Schatz, David G, Hu, Jiazhi. . RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination. In Cell reports, 37, 109824. doi:10.1016/j.celrep.2021.109824. https://pubmed.ncbi.nlm.nih.gov/34644584/

4. Brecht, Ryan M, Liu, Catherine C, Beilinson, Helen A, Slavoff, Sarah A, Schatz, David G. 2020. Nucleolar localization of RAG1 modulates V(D)J recombination activity. In Proceedings of the National Academy of Sciences of the United States of America, 117, 4300-4309. doi:10.1073/pnas.1920021117. https://pubmed.ncbi.nlm.nih.gov/32047031/

5. Villa, A, Santagata, S, Bozzi, F, Imberti, L, Notarangelo, L D. . Omenn syndrome: a disorder of Rag1 and Rag2 genes. In Journal of clinical immunology, 19, 87-97. doi:. https://pubmed.ncbi.nlm.nih.gov/10226883/

6. Liu, Yuchen, Jiang, Nan, Liu, Wenzhi, Li, Zhong, Fan, Yuding. 2022. Rag1 and Rag2 Gene Expressions Identify Lymphopoietic Tissues in Larvae of Rice-Field Eel (Monopterus albus). In International journal of molecular sciences, 23, . doi:10.3390/ijms23147546. https://pubmed.ncbi.nlm.nih.gov/35886885/