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Stem Cell Related Patent Number US5859312
| Title: | Transgenic non-human animals having targeting endogenous lymphocyte transduction genes and cognate human transgenes | | Inventors: | Littman, Daniel; San Francisco, CA, USA
Sawada, Shinichiro; San Francisco, CA, USA
Killeen, Nigel; San Francisco, CA, USA | | Summary: | This invention introduces a novel transgenic nonhuman mammal with a disrupted lymphocyte transduction gene and a targeting construct for disruption or for human gene insertion. Described herein is a transgenic mouse having a diploid genome with a functionally disrupted endogenous CD4 locus such that the disruption is in the nucleotide sequence of one or more coding region exons. Further disclosed are methods by which a gene encoding human CD4 is integrated into the genome of the mouse wherein the human CD4 gene is transcriptionally regulated by an operably linked human CD4 promoter and an upstream T cell specific enhancer, and wherein the mouse is shown to express a human CD4 protein in a T cell-specific manner. Targeting constructs are provided, by which such transgenic stem cells and animals may be produced, as are methods and targeting constructs for inactivating or suppressing the expression of endogenous lymphocyte transduction gene loci, transgenes encoding heterologous lymphocyte transduction proteins, and nonhuman mammals that express a human lymphocyte transduction protein and lack expression of a cognate murine lymphocyte transduction protein. Experimental applications are provided for the production of mice which cannot express murine CD4 or CD2 as therapeutic models for the treatment of human disease. | | Abstract: | The invention provides transgenic non-human animals and transgenic non-human mammalian cells having at least one functionally disrupted lymphocyte transduction locus, particularly a CD4 locus, targeting constructs used to produce such transgenic stem cells and animals, methods and targeting constructs for inactivating or suppressing expression of endogenous lymphocyte transduction gene loci, transgenes encoding heterologous lymphocyte transduction proteins, and nonhuman animals that express a human lymphocyte transduction protein and lack expression of a cognate murine lymphocyte transduction protein. | | US Patent Website: | Click Here for Full Text of Patent | | Title Number: | US5859312 | | Application Number: | US1996000676828 | | Date Filed: | 08/07/1996 | | Date Published: | 12/01/1999 | | Assignee: | The Regents of the University of California, Oakland, CA, USA |
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