ArticleProceedings of the National Academy of Sciences of the United States of America1993
RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
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Who cites it
172 citing papers in PubMed, 403 citations in OpenAlex.
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- Considerations for recipient male selection in a livestock Surrogate Sire breeding strategy.The Journal of reproduction and development · 2026Review
- Human-Mouse Chimerism for Organogenesis Without Neural or Germline Contributions.International journal of biological sciences · 2026Article
- Generation of parathyroid glands from pluripotent stem cells.Endocrine journal · 2025Review
- Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies.Neuron · 2025Review
- Blastocyst complementation: current progress and future directions in xenogeneic organogenesis.Stem cell research & therapy · 2025Review
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- Foxa1 disruption enhances human cell integration in human-mouse interspecies chimeras.Cell and tissue research · 2025Article
- An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.Science translational medicine · 2025Article
- Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development.iScience · 2024Article
- Producing Human Livers From Human Stem Cells Via Blastocyst Complementation.Current opinion in biomedical engineering · 2024Article
- Parathyroid Gland Generation from Pluripotent Stem Cells.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Generation of salivary glands derived from pluripotent stem cells via conditional blastocyst complementation.Cell reports · 2024Article
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- Vaccination induces broadly neutralizing antibody precursors to HIV gp41.Nature immunology · 2024Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We describe a system to evaluate the function of lymphocyte-specific and generally expressed genes in the differentiation and/or function of lymphocytes. RAG-2 (recombination-activating gene 2)-deficient mice have no mature B and T lymphocytes due to the inability to initiate VDJ recombination. Blastocysts from RAG-2-deficient mice generate animals with no mature B and T cells following implantation into foster mothers. However, injection of normal ES cells into RAG-2-deficient blastocysts leads to the generation of somatic chimeras with mature B and T cells all of which derive from the injected ES cells (referred to as RAG-2-deficient blastocyst complementation). Complementation of RAG-2-deficient blastocysts with mutant ES cells heterozygous for a targeted mutation that deletes all immunoglobulin heavy-chain joining (JH) gene segments (JH+/-) also leads to generation of chimeras with normal B and T cells. However, complementation with ES cells homozygous for the JH mutation (JH-/-) generates animals with normal T cells but no B cells, due to a block in B-cell development at a very early stage. Transfection of a functionally assembled mu heavy-chain gene into the JH-/- ES cells prior to blastocyst injection rescues the JH-/- mutation and allows the generation of both mature T and mature B cells. The rescued B cells express IgM but not IgD and respond normally to bacterial lipopolysaccharide stimulation by proliferating and by secreting IgM.
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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.