Germ-line transmission of a disrupted β2microglobulin gene produced by homologous recombination in embryonic stem cells (original) (raw)

Nature volume 342, pages 435–438 (1989)Cite this article

Abstract

MAJOR histocompatibility complex (MHC) class I molecules are integral membrane proteins present on virtually all vertebrate cells and consist of a heterodimer between the highly polymorphic _α_-chain and the _β_2microglobulin (β2-m) protein of relative molecular mass 12,000 (ref. 1). These cell-surface molecules play a pivotal part in the recognition of antigens, the cytotoxic response of T cells, and the induction of self tolerance1,2. It is possible, however, that the function of MHC class I molecules is not restricted to the immune system, but extends to a wide variety of biological reactions including cell–cell interactions. For example, MHC class I molecules seem to be associated with various cell-surface proteins, including the receptors for insulin, epidermal growth factor, luteinizing hormone and the _β_-adrenergic receptor3–6. In mice, class I molecules are secreted in the urine and act as highly specific olfactory cues which influence mating preference7, 8. The β2-m protein has also been identified as the smaller component of the Fc receptor in neonatal intestinal cells9, and it has been suggested that the protein induces collagenase in fibrob-lasts10. Cells lacking β2-m are deficient in the expression of MHC class I molecules, indicating that the association with β2-m is crucial for the transport of MHC class I molecules to the cell surface1. The most direct means of unravelling the many biological functions of _β2-m_is to create a mutant mouse with a defective _β2-m_gene. We have now used the technique of homologous recombination to disrupt the _β2-m_gene. We report here that introduction of a targeting vector into embryonic stem cells resulted in _β2-m_gene disruption with high frequency. Chimaeric mice derived from blastocysts injected with mutant embryonic stem cell clones transmit the mutant allele to their offspring.

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Nine Cambridge Center,
    Maarten Zijlstra, En Li & Rudolf Jaenisch
  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA
    Maarten Zijlstra, En Li & Rudolf Jaenisch
  3. Department of Biology, University of California, B-022 Bonner Hall, San Diego, La Jolla, California, 92093, USA
    Fereydoun Sajjadi & Suresh Subramani

Authors

  1. Maarten Zijlstra
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  2. En Li
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  3. Fereydoun Sajjadi
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  4. Suresh Subramani
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  5. Rudolf Jaenisch
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Zijlstra, M., Li, E., Sajjadi, F. et al. Germ-line transmission of a disrupted _β_2microglobulin gene produced by homologous recombination in embryonic stem cells.Nature 342, 435–438 (1989). https://doi.org/10.1038/342435a0

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