Flox Mice

About

Description A portion of the cells of the mouse undergo directed somatic recombination resulting in a mouse that is a mosaic for homozygous knockout of both p53 and NF1 genes (p53-NF1 MADM mouse). The homozygous null cells resulting from the somatic recombination also express a detectable green fluorescent protein, and the resulting sibling cells, which are wild type for both p53 and NF1 (p53-NF1 MADM mouse), express a red fluorescent protein. The mosaic nature of the mouse for cells that are homozygous null (for p53, NF1) more closely models the loss of heterozygosity (LOH) of tumor suppressor genes (TSG) that frequently contributes to tumor development than conventional mouse knockout models (where all of the cells in the mouse or in a particular tissue are homozygous null). In addition, the differential detectable labeling of homozygous null and wild type cells allows the development and fate of tumor cells and normal cells to be followed either in vitro or in vivo.  These mice are being used to study the entire course of gliomagenesis arising from sporadic p53/NF1 double mutant cells in the brain. The single-cell resolution and built-in control provided by MADM revealed that, among all mutant cell types, oligodendrocyte precursor cells (OPCs) are the only drastically over-expanding and proliferative cell lineage from pre-transformed stages to full malignancy. Surprisingly, purified glioma tumor propagating cells (TPCs) manifested unusual plasticity, displaying not only salient OPC features but also stem cell signatures. (Cell. 2011 Jul 22;146(2):209-21).