Transgenic mice expressing HIV-1 in immune cells
AssigneeInstitut de Recherches Cliniques de Montreal
InventorsPaul Jolicoeur, Zaher Hanna, Denis G. Kay
Life of this patent
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Abstract
The present invention relates to a transgenic mouse to serve as a small animal model of AIDS which comprises at least a DNA sequence coding for HIV-1 nef or a HIV-1 DNA genome essentially consisting in entire HIV-1 coding sequences under the control of the human CD4 gene promoter flanked by the enhancer of the mouse CD4 gene for expression in T cells and in cells of monocyte/microphage lineage. There is also provided a method to screen for therapeutic agents for the treatment of AIDS, which comprises the steps of: a) administering the therapeutic agent to the mouse of the present invention; and b) determining the effects of the therapeutic agent.
Claims15
A transgenic or chimeric mouse to serve as a small animal model of AIDS wherein at least the somatic cells of said mouse comprises a transgene comprising a DNA sequence encoding HIV-1 in operable linkage with the human CD4 promoter flanked by the enhancer of the mouse CD4 gene, wherein said transgene is expressed in T-cells and in cells of monocyte/macrophage lineage, and wherein expression of said transgene is sufficient to effect phenotypic changes consistent with AIDS pathology.
A transgenic mouse to serve as a small animal model of AIDS in which at least the somatic cells comprise a transgene that comprises:
- a) a HIV-1 coding sequence;
- and
- b) a human CD4 gene promoter operatively linked to said HIV-1 coding sequence, wherein said promoter is flanked by the enhancer of the mouse CD4 gene for expression in T-cells and in cells of monocyte/macrophage lineage, and
- wherein said transgene is introduced into said mouse or an ancestor thereof as a single transgene, and wherein expression of said transgene is sufficient to effect phenotypic changes consistent with AIDS pathology.
A method for producing a transgenic mouse to serve as a small animal model of AIDS, which comprises the steps of:
- a) transferring a transgene into a mouse fertilized oocyte, wherein the transgene comprises:
- i) a HIV-1 coding sequence;
- and
- ii) a human CD4 gene promoter operatively linked to said HIV-1 coding sequence,
- wherein said promoters flanked by the enhancer of the mouse CD4 gene for expression in T-cells and in cells of monocyte/macrophage lineage;
- b) transferring a fertilized oocyte containing the transgene to the uterus of a female mouse;
- c) maintaining the mouse of step b) such that said mouse becomes pregnant with an embryo derived from said fertilized oocyte, and allowing said embryo to develop to term;
- and
- d) selecting a transgenic mouse whose genome comprises said transgene;
- wherein expression of said transgene is sufficient to effect phenotypic changes consistent with AIDS pathology.
A chimeric mouse to serve as a small animal model of AIDS in which at least the somatic cells comprise a transgene that comprises:
- a) a HIV-1 coding sequence;
- and
- b) a human CD4 gene promoter operatively linked to said HIV-1 coding sequence, wherein said promoter is flanked by the enhancer of the mouse CD4 gene for expression in T-cells and in cells of monocyte/macrophage lineage, and
- wherein said transgene is introduced into said mouse or an ancestor thereof as a single transgene, and wherein expression of said transgene is sufficient to effect phenotypic changes consistent with AIDS pathology.
A method for producing a chimeric mouse to serve as a small animal model of AIDS, which comprises the steps of:
- a) transferring a transgene into a mouse embryonic stem cell line, wherein the transgene comprises:
- i) a HIV-1 coding sequence;
- and
- ii) a human CD4 gene promoter operatively linked to said HIV-1 coding sequence,
- wherein said promoter is flanked by the enhancer of the mouse CD4 gene for expression in T-cells and in cells of monocyte/macrophage lineage;
- b) selecting an embryonic stem cell line whose genome comprises said transgene;
- c) introducing the embryonic stem cell line of step b) into a viable blastocyst;
- d) transferring the injected blastocyst having the embryonic cells into a pseudopregnant female mouse;
- e) screening for a chimeric mouse born to the female mouse which include the transgene;
- wherein expression of said transgene in said chimeric is sufficient to effect phenotypic changes consistent with AIDS pathology.
Dependencies are inferred from the claim text.