ArticleBlood2009
Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- B cell abnormalities and autoantibody production in patients with partial RAG deficiency.Frontiers in immunology · 2023Review
- Rare immune diseases paving the road for genome editing-based precision medicine.Frontiers in genome editing · 2023Review
- RAG1 splicing mutation causes enhanced B cell differentiation and autoantibody production.JCI insight · 2021Article
- RAG deficiencies: Recent advances in disease pathogenesis and novel therapeutic approaches.European journal of immunology · 2021Review
- Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side.Pharmaceutics · 2020Review
- Successful Preclinical Development of Gene Therapy for Recombinase-Activating Gene-1-Deficient SCID.Molecular therapy. Methods & clinical development · 2020Article
- Innovative Cell-Based Therapies and Conditioning to Cure RAG Deficiency.Frontiers in immunology · 2020Review
- CD3εFrontiers in immunology · 2020Article
- The R229Q mutation of Rag2 does not characterize severe immunodeficiency in mice.Scientific reports · 2019Article
- Efficient Production of Biallelic RAG1 Knockout Mouse Embryonic Stem Cell Using CRISPR/Cas9.Iranian journal of biotechnology · 2019Article
- RAG gene defects at the verge of immunodeficiency and immune dysregulation.Immunological reviews · 2019Review
- HypomorphicBlood · 2018Article
- MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress.Cancer research · 2017Article
- GATA3 Abundance Is a Critical Determinant of T Cell Receptor β Allelic Exclusion.Molecular and cellular biology · 2017Article
- Article
- Rapid generation of novel models of RAG1 deficiency by CRISPR/Cas9-induced mutagenesis in murine zygotes.Oncotarget · 2016Article
- Programmed DNA breaks in lymphoid cells: repair mechanisms and consequences in human disease.Immunology · 2016Review
- Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency.The Journal of clinical investigation · 2015Article
- Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus and erosive arthritis.The Journal of allergy and clinical immunology · 2015Article
- A hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency.The Journal of allergy and clinical immunology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The RAG1/2 endonuclease initiates programmed DNA rearrangements in progenitor lymphocytes by generating double-strand breaks at specific recombination signal sequences. This process, known as V(D)J recombination, assembles the vastly diverse antigen receptor genes from numerous V, D, and J coding segments. In vitro biochemical and cellular transfection studies suggest that RAG1/2 may also play postcleavage roles by forming complexes with the recombining ends to facilitate DNA end processing and ligation. In the current study, we examine the in vivo consequences of a mutant form of RAG1, RAG1-S723C, that is proficient for DNA cleavage, yet exhibits defects in postcleavage complex formation and end joining in vitro. We generated a knockin mouse model harboring the RAG1-S723C hypomorphic mutation and examined the immune system in this fully in vivo setting. RAG1-S723C homozygous mice exhibit impaired lymphocyte development and decreased V(D)J rearrangements. Distinct from RAG nullizygosity, the RAG1-S723C hypomorph results in aberrant DNA double-strand breaks within rearranging loci. RAG1-S723C also predisposes to thymic lymphomas associated with chromosomal translocations in a p53 mutant background, and heterozygosity for the mutant allele accelerates age-associated immune system dysfunction. Thus, our study provides in vivo evidence that implicates aberrant RAG1/2 activity in lymphoid tumor development and premature immunosenescence.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.