C57BL/6JCya-Dclre1c^em1/Cya

Dclre1c, also known as the gene encoding Artemis, is crucial for V(D)J recombination, an essential process in the differentiation and maturation of T and B cells. It is also involved in the repair of DNA double-strand breaks via the non-homologous end-joining (NHEJ) pathway [4,5,6,7].

In a phase 1-2 clinical study, lentiviral gene therapy using autologous CD34+ cells transfected with DCLRE1C was carried out in infants with Artemis-deficient severe combined immunodeficiency (ART-SCID). The therapy led to genetically corrected and functional T and B cells [1]. NK cells from DCLRE1C-deficient severe combined immunodeficiency (SCID) patients were found to be functional in inhibiting HCMV transmission between cells in vitro [2]. Dclre1c-deficient mice with an NOD genetic background, generated using CRISPR/Cas9-mediated gene editing, exhibited a radiosensitive SCID phenotype with reduced T and B lymphocyte populations and were successfully engrafted with cell lines and patient-derived tumor xenografts [3].

In conclusion, Dclre1c is essential for V(D)J recombination and DNA repair, playing a key role in the development and function of the immune system. The study of Dclre1c-deficient mouse models and human patient-based research has provided insights into its role in immunodeficiency diseases, such as ART-SCID, and has potential implications for gene therapy and understanding immune-related disorders [1,2,3].

References:

1. Cowan, Morton J, Yu, Jason, Facchino, Janelle, McIvor, R Scott, Puck, Jennifer M. . Lentiviral Gene Therapy for Artemis-Deficient SCID. In The New England journal of medicine, 387, 2344-2355. doi:10.1056/NEJMoa2206575. https://pubmed.ncbi.nlm.nih.gov/36546626/

2. Wu, Zeguang, Subramanian, Narmadha, Jacobsen, Eva-Maria, Hönig, Manfred, Mertens, Thomas. 2019. NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV. In Microorganisms, 7, . doi:10.3390/microorganisms7110546. https://pubmed.ncbi.nlm.nih.gov/31717670/

3. Bin, Yixiao, Wei, Sanhua, Chen, Ruo, Chen, Zhinan, Zhang, Hai. 2024. Dclre1c-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research. In Biomolecules, 14, . doi:10.3390/biom14020180. https://pubmed.ncbi.nlm.nih.gov/38397417/

4. Mou, Wenjun, Gao, Liwei, He, Jianxin, Xu, Baoping, Gui, Jingang. 2021. Compound heterozygous DCLRE1C mutations lead to clinically typical Severe Combined Immunodeficiency presenting with Graft Versus Host Disease. In Immunogenetics, 73, 425-434. doi:10.1007/s00251-021-01219-4. https://pubmed.ncbi.nlm.nih.gov/34406419/

5. Watanabe, Go, Lieber, Michael R, Williams, Dewight R. . Structural analysis of the basal state of the Artemis:DNA-PKcs complex. In Nucleic acids research, 50, 7697-7720. doi:10.1093/nar/gkac564. https://pubmed.ncbi.nlm.nih.gov/35801871/

6. Volk, Timo, Pannicke, Ulrich, Reisli, Ismail, Schwarz, Klaus, Grimbacher, Bodo. 2015. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. In Human molecular genetics, 24, 7361-72. doi:10.1093/hmg/ddv437. https://pubmed.ncbi.nlm.nih.gov/26476407/

7. Pannicke, Ulrich, Hönig, Manfred, Schulze, Ilka, Friedrich, Wilhelm, Schwarz, Klaus. . The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. In Human mutation, 31, 197-207. doi:10.1002/humu.21168. https://pubmed.ncbi.nlm.nih.gov/19953608/