Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A procedure of reversible immortalization of primary cells was devised by retrovirus-mediated transfer of an oncogene that could be subsequently excised by site-specific recombination. This study focused on the early stages of immortalization: global induction of proliferation and life span extension of cell populations. Comparative analysis of Cre/LoxP and FLP/FRT recombination in this system indicated that only Cre/LoxP operates efficiently in primary cells. Pure populations of cells in which the oncogene is permanently excised were obtained, following differential selection of the cells. Cells reverted to their preimmortalized state, as indicated by changes in growth characteristics and p53 levels, and their fate conformed to the telomere hypothesis of replicative cell senescence. By permitting temporary and controlled expansion of primary cell populations without retaining the transferred oncogene, this strategy may facilitate gene therapy manipulations of cells unresponsive to exogenous growth factors and make practical gene targeting by homologous recombination in somatic cells. The combination of retroviral transfer and site-specific recombination should also extend gene expression studies to situations previously inaccessible to experimentation.
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PMID:Reversible immortalization of mammalian cells mediated by retroviral transfer and site-specific recombination. 879 38

We used a recently developed method to produce mutant alleles of five endogenous Drosophila genes, including the homolog of the p53 tumor suppressor. Transgenic expression of the FLP site-specific recombinase and the I-SceI endonuclease generates extrachromosomal linear DNA molecules in vivo. These molecules undergo homologous recombination with the corresponding chromosomal locus to generate targeted alterations of the host genome. The results address several questions about the general utility of this technique. We show that genes not near telomeres can be efficiently targeted; that no knowledge of the mutant phenotype is needed for targeting; and that insertional mutations and allelic substitutions can be easily produced.
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PMID:Targeted mutagenesis by homologous recombination in D. melanogaster. 1208 94

Genetic mosaics produced by FLP/FRT induced mitotic recombination have been widely used in Drosophila to study gene function in development. Recently, the Cre/loxP system has been applied to induce mitotic recombination in mouse embryonic stem cells and in many adult mouse tissues. We have used this strategy to generate a previously undescribed p53 mouse model in which expression of a ubiquitously expressed recombinase in a heterozygous p53 knockout animal produces mitotic recombinant clones homozygous for the p53 mutation. The induction of loss of heterozygosity in a few cells in an otherwise normal tissue mimics genetic aspects of tumorigenesis more closely than existing models and has revealed the possible cell autonomous nature of Wnt3. Our results suggest that inducible mitotic recombination can be used for clonal analysis of mutants in the mouse.
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PMID:Induced mitotic recombination of p53 in vivo. 1736 May 8