ArticlePloS one2011
Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 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.
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Who cites it
78 citing papers in PubMed, 173 citations in OpenAlex.
- Application of CRISPR/Cas gene editing for infectious disease control in poultry.Open life sciences · 2025Review
- Genome-edited rabbits: Unleashing the potential of a promising experimental animal model across diverse diseases.Zoological research · 2024Review
- Development Features on the Selection of Animal Models for Teratogenic Testing.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Outlook on genome editing application to cattle.Journal of veterinary science · 2024Review
- Versatile generation of precise gene edits in bovines using SEGCPN.BMC biology · 2023Article
- The history, use, and challenges of therapeutic somatic cell and germline gene editing.Fertility and sterility · 2023Review
- Perspectives in Genome-Editing Techniques for Livestock.Animals : an open access journal from MDPI · 2023Review
- How genome editing changed the world of large animal research.Frontiers in genome editing · 2023Review
- Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus.Viruses · 2022Review
- Hybridoma technology: is it still useful?Current research in immunology · 2021Review
- Genetically Modified Rabbits for Cardiovascular Research.Frontiers in genetics · 2021Review
- Genome engineering technologies in rabbits.Journal of biomedical research · 2020Article
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.Signal transduction and targeted therapy · 2020Review
- Meeting report of the OECD conference on "Genome Editing: Applications in Agriculture-Implications for Health, Environment and Regulation".Transgenic research · 2019Article
- Generation of genetically-engineered animals using engineered endonucleases.Archives of pharmacal research · 2018Review
- Engineering altered protein-DNA recognition specificity.Nucleic acids research · 2018Review
- The wide utility of rabbits as models of human diseases.Experimental & molecular medicine · 2018Review
- Cattle with a precise, zygote-mediated deletion safely eliminate the major milk allergen beta-lactoglobulin.Scientific reports · 2018Article
- Principles and Applications of Rabbit Models for Atherosclerosis Research.Journal of atherosclerosis and thrombosis · 2018Review
- Genetically engineered pigs as models for human disease.Disease models & mechanisms · 2018Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs) introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM) locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM(+) and IgG(+) B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields.
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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.