| First Author | Ott de Bruin L | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 11 | Pages | 12962-74 |
| PubMed ID | 26887046 | Mgi Jnum | J:265589 |
| Mgi Id | MGI:6201637 | Doi | 10.18632/oncotarget.7341 |
| Citation | Ott de Bruin L, et al. (2016) Rapid generation of novel models of RAG1 deficiency by CRISPR/Cas9-induced mutagenesis in murine zygotes. Oncotarget 7(11):12962-74 |
| abstractText | Mutations in the Recombination Activating Gene 1 (RAG1) can cause a wide variety of clinical and immunological phenotypes in humans, ranging from absence of T and B lymphocytes to occurrence of autoimmune manifestations associated with expansion of oligoclonal T cells and production of autoantibodies. Although the mechanisms underlying this phenotypic heterogeneity remain poorly understood, some genotype-phenotype correlations can be made. Currently, mouse models of Rag deficiency are restricted to RAG1-/- mice and to knock-in models carrying severe missense mutations. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system is a novel and powerful gene-editing strategy that permits targeted introduction of DNA double strand breaks with high efficiency through simultaneous delivery of the Cas9 endonuclease and a guide RNA (gRNA). Here, we report on CRISPR-based, single-step generation and characterization of mutant mouse models in which gene editing was attempted around residue 838 of RAG1, a region whose functional role had not been studied previously. |
