ArticleBMC immunology2012
Zinc-finger nuclease mediated disruption of Rag1 in the LEW/Ztm rat.
Article in BMC immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Early Deficient Lactation Differentially Affects Neonatal Thymic Cortical Development and Humoral Immune Responses in Rats.International journal of molecular sciences · 2026Article
- Advances and applications of genome-edited animal models for severe combined immunodeficiency.Zoological research · 2025Review
- In Vivo Modeling of Human Breast Cancer Using Cell Line and Patient-Derived Xenografts.Journal of mammary gland biology and neoplasia · 2022Review
- Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models.Frontiers in genetics · 2021Review
- Tools for experimental and computational analyses of off-target editing by programmable nucleases.Nature protocols · 2021Review
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Severe combined immunodeficiency pig as an emerging animal model for human diseases and regenerative medicines.BMB reports · 2019Review
- Generation of genetically-engineered animals using engineered endonucleases.Archives of pharmacal research · 2018Review
- Rat embryonic stem cells create new era in development of genetically manipulated rat models.World journal of stem cells · 2015Review
- Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- An online bioinformatics tool predicts zinc finger and TALE nuclease off-target cleavage.Nucleic acids research · 2014Article
- Derivation and characterization of mouse embryonic stem cells from permissive and nonpermissive strains.Nature protocols · 2014Article
- Rats are the smart choice: Rationale for a renewed focus on rats in behavioral genetics.Neuropharmacology · 2014Article
- Article
- Evaluation of novel design strategies for developing zinc finger nucleases tools for treating human diseases.Biotechnology research international · 2014Article
- Genetic mutation of recombination activating gene 1 in Dahl salt-sensitive rats attenuates hypertension and renal damage.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Article
- Progress and prospects for genetic modification of nonhuman primate models in biomedical research.ILAR journal · 2013Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEngineered zinc-finger nucleases (ZFN) represented an innovative method for the genome manipulation in vertebrates. ZFN introduced targeted DNA double strand breaks (DSB) and initiated non-homologous end joining (NHEJ) after pronuclear or cytoplasmatic microinjection into zygotes. Resulting frame shift mutations led to functional gene ablations in zebra fish, mice, pigs and also in laboratory rats. Therefore, we targeted the rat Rag1 gene essential for the V(D)J recombination within the immunoglobulin production process and for the differentiation of mature B and T lymphocytes to generate an immunodeficient rat model in the LEW/Ztm strain.
resultsAfter microinjection of Rag1 specific ZFN mRNAs in 623 zygotes of inbred LEW/Ztm rats 59 offspring were born from which one carried a 4 bp deletion. This frame shift mutation led to a premature stop codon and a subsequently truncated Rag1 protein confirmed by the loss of the full-length protein in Western Blot analysis. Truncation of the Rag1 protein was characterized by the complete depletion of mature B cells. The remaining T cell population contained mature CD4+/CD3+/TCRαβ+ as well as CD8+/CD3+/TCRαβ+ positive lymphocytes accompanied by a compensatory increase of natural killer cells in the peripheral blood. Reduction of T cell development in Rag1 mutant rats was associated with a hypoplastic thymus that lacked follicular structures. Histological evaluation also revealed the near-complete absence of lymphocytes in spleen and lymph nodes in the immunodeficient Rag1 mutant rat.
conclusionThe Rag1 mutant rat will serve as an important model for transplantation studies. Furthermore, it may be used as a model for reconstitution experiments related to the immune system, particularly with respect to different populations of human lymphocytes, natural killer cells and autoimmune phenomena.
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