Knockout mouse for the tumor suppressor gene ANX7
AssigneeThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
InventorsMeera Srivastava, Harvey B. Pollard
Life of this patent
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Abstract
A knockout transgenic mouse containing a nonfunctional allele of the tumor suppressing gene, annexin VII. This mouse is used as a screening model for potential therapeutic agents useful in the treatment of tumors resulting from an annexin tumor suppressor disease.
Claims19
A transgenic mouse having cells comprising a chromosomally incorporated transgene that comprises a detectable marker sequence, wherein one allele of a genomic Anx VII gene is functionally disrupted by said transgene, wherein said transgenic mouse exhibits an increased susceptibility to formation of tumors as compared to a wild type mouse, and wherein said tumors are one or more of insulinoma, hepatocellular carcinoma, and lymphoma of the thymus.
A transgenic mouse embryo having cells comprising a chromosomally incorporated transgene that comprises a detectable marker sequence, wherein at least one allele of the Anx VII gene is functionally disrupted by said transgene, and wherein said mouse embryo is aged E10 or less.
A method for generating a transgenic mouse having an endogenous Anx VII gene that is functionally disrupted, comprising the steps of:
- a) constructing a transgene construct containing
- (i) a recombination region having all or a portion of the endogenous Anx VII gene, and
- (ii) a marker sequence, which provides a detectable signal for identifying the presence of the transgene in a cell;
- b) transferring the transgene into embryonic stem cells of a mouse by the process of homologous recombination;
- c) selecting embryonic stem cells having a correctly targeted homologous recombination between the transgene construct and the Anx VII gene;
- d) transferring the cells of step (c) into a blastocyst and implanting the resulting chimeric blastocyst into a female mouse;
- and
- e) selecting offspring harboring an endogenous Anx VII gene allele comprising the correctly targeted recombination.
A method for generating an isolated transgenic mouse embryonic stem cell having an endogenous Anx VIl gene that is functionally disrupted, comprising the steps of:
- a) constructing a transgene construct containing
- (i) a recombination region having all or a portion of the endogenous Anx VII gene, and
- (ii) a marker sequence which provides a detectable signal for identifying the presence of the transgene in a cell;
- b) transferring the transgene into an embryonic stem cell of a mouse by the process of homologous recombination;
- and
- c), selecting a mouse embryonic stem cell having a correctly targeted homologous recombination between the transgene construct and the endogenous Anx VII gene.
A transgene construct comprising a recombination region having all or a portion of an endogenous Anx VII gene;
- wherein the Anx VII gene comprises an inserted marker sequence which provides a detectable signal for identifying the presence of the transgene in a mammalian cell;
- wherein the Anx VII gene is functionally disrupted.
Dependencies are inferred from the claim text.