Cell Genesys, Inc.

The University of North Carolina at Chapel Hill

The United States of America As Represented by the Department of Health

Oliver Smithies

Beverly H Koller

Raju S Kucherlapati

Robert B Dubridge

Daniel J Capon

Steven R Williams

Gary Greenburg

Mariona Lourdes De Rafael

Dennis Bryant Lubahn

Mariona Lourdes Arbones De Rafael

Kenneth S Korach

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the &bgr; -microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Homologous recombination for universal donor cells and chimeric mammalian hosts

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2- microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as allogeneic donor cells. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Homologous recombination for allogeneic donor cells

The present invention provides a mutant non-human vertebrate, in which all or some of the germ and somatic cells contain a mutation in at least one steroid hormone receptor allele, which mutation is introduced into the vertebrate, or an ancestor of the vertebrate, at an embryonic stage, and which mutation produces a phenotype in the vertebrate characterized by a deficit of functional steroid hormone receptors encoded by the allele. Also disclosed are related methods and constructs.

Mutant mice having a deficit of functional estrogen receptors

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, each of the .beta..sub.2- microglobulin gene and the IFN-.gamma.R gene is inactivated for reducing or eliminating the expression of functional MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Homologous recombination for universal donor cells and chimeric

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2 -microglobulin gene is inactivated for reducing or eliminating Class I MHC antigens. The resulting cells may be used as universal donors. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs.

Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2 -microglobulin gene is inactivated for reducing or eliminating Class I MHC antigens. The resulting cells may be used as universal donors. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies.

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Chapel Hill, NC, United States of America

Oliver Smithies