Mosaic knockout mouse tumor models and methods or use
AssigneesThe State of Oregon acting by and through the State Board of Higher Education on behalf of, University of Oregon
InventorsHui Zong, Chong Liu
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Abstract
Disclosed herein are transgenic mouse tumor models. A portion of the cells of the disclosed transgenic mice undergo directed somatic recombination and the mouse is therefore a mosaic for homozygous knockout of p53, NF1, or both p53 and NF1 genes. The homozygous null cells resulting from the somatic recombination also express a detectable fluorescent protein, and the resulting sibling cells, which are wild type for p53, NF1, or both p53 and NF1, express a different detectable fluorescent protein. Also disclosed herein are methods of identifying compounds for treating or preventing a tumor, using the disclosed transgenic mice.
Claims22
A transgenic mouse the genome of which comprises:
- a) a first nucleic acid molecule comprising a first promoter operably linked to a nucleic acid molecule encoding an N-terminal portion of a green fluorescent protein (GFP) and a C-terminal portion of a tdTomato (tdT) fluorescent protein, wherein the N-terminal portion of the GFP and the C-terminal portion of the tdT protein are separated by a β-globin intron comprising a first loxP site, and wherein the first nucleic acid molecule is present at a locus of a first chromosome 11 of a chromosome 11 pair;
- b) a second nucleic acid molecule comprising a second promoter operably linked to a nucleic acid molecule encoding an N-terminal portion of the tdT protein and a C-terminal portion of the GFP, wherein the N-terminal portion of the tdT protein and the C-terminal portion of the GFP are separated by the β-globin intron comprising a second loxP site, and wherein the second nucleic acid molecule is present at the homologous locus of the second chromosome 11 of the chromosome 11 pair;
- c) a mutated gene selected from the group consisting of a heterozygous null mutation in the p53 gene on the second chromosome 11 of the chromosome 11 pair, a heterozygous floxed neurofibromatosis type 1 (NF1) gene on the second chromosome 11 of the chromosome 11 pair, and a combination thereof;
- and
- d) a third nucleic acid molecule encoding a Cre recombinase operably linked to a third promoter, wherein Cre recombinase-promoted somatic recombination between the first and second loxP sites occurs in at least one cell of the transgenic mouse resulting in at least a first cell comprising a first recombined nucleic acid molecule encoding a functional GFP and a homozygous null mutated gene and at least a second cell comprising a second recombined nucleic acid molecule encoding a functional tdT protein and a homozygous wild type mutated gene.
A transgenic mouse the genome of which comprises:
- a) a nucleic acid molecule comprising a promoter operably linked to a nucleic acid molecule encoding an N-terminal portion of a tdTomato (tdT) fluorescent protein and a C-terminal portion of a green fluorescent protein (GFP), wherein the N-terminal portion of the tdT protein and the C-terminal portion of the GFP are separated by a β-globin intron comprising a first loxP site, and wherein the first nucleic acid molecule is present at a locus of a both chromosomes 11 of a chromosome 11 pair;
- b) a heterozygous null mutation in the p53 gene on a first chromosome 11 of the chromosome 11 pair;
- and
- c) a heterozygous floxed neurofibromatosis type 1 (NF1) gene on the first chromosome 11 of the chromosome 11 pair
A transgenic mouse the genome of which comprises a first nucleic acid molecule comprising a first promoter operably linked to a nucleic acid molecule encoding an N-terminal portion of a green fluorescent protein (GFP) and a C-terminal portion of a tdTomato (tdT) fluorescent protein, wherein the N-terminal portion of the GFP and the C-terminal portion of the tdT protein are separated by a β-globin intron comprising a first loxP site, and wherein the nucleic acid molecule is present at a locus i of both chromosomes 11 of a chromosome 11 pair.
A transgenic mouse the genome of which comprises:
- a) a nucleic acid molecule comprising a promoter operably linked to a nucleic acid molecule encoding an N-terminal portion of a green fluorescent protein (GFP) and a C-terminal portion of a tdTomato (tdT) fluorescent protein, wherein the N-terminal portion of the GFP and the C-terminal portion of the tdT protein are separated by a β-globin intron comprising a first loxP site, and wherein the first nucleic acid molecule is present at a locus of a both chromosomes 11 of a chromosome 11 pair;
- b) a heterozygous null mutation in the p53 gene on a first chromosome 11 of the chromosome 11 pair;
- and
- c) a heterozygous floxed neurofibromatosis type 1 (NF1) gene on the first chromosome 11 of the chromosome 11 pair
A transgenic mouse the genome of which comprises a first nucleic acid molecule comprising a first promoter operably linked to a nucleic acid molecule encoding an N-terminal portion of a tdTomato (tdT) fluorescent protein and a C-terminal portion of a green fluorescent protein (GFP), wherein the N-terminal portion of the tdT protein and the C-terminal portion of the GFP are separated by a β-globin intron comprising a first loxP site, and wherein the nucleic acid molecule is present at a locus of both chromosomes 11 of a chromosome 11 pair.
Dependencies are inferred from the claim text.