A Transgenic Mouse Line Expressing Green Fluorescent Protein in Cells Containing Endogenous Notch Pathway Activation
The TNR1 mouse line (Transgenic Notch Reporter) contains exogenous DNA stably integrated into the genome. The transgenic sequence includes binding sites for a DNA binding protein CBF1 (also known as RBP-J) upstream of a basal SV40 promoter and a cDNA encoding the enhanced green fluorescent protein (GFP). Upon activation of the Notch pathway, CBF1 is converted from a transcriptional repressor into a transcriptional activator thus driving GFP expression, causing cells to become green, permitting identification and isolation. The Notch/CBF1 signaling pathway is of fundamental importance in a wide variety of tissues throughout embryonic development and in the adult. The ability to prospectively identify and isolate cells harboring active Notch/CBF1 signaling provides a powerful means to study and manipulate these cells. Since Notch/CBF1 signaling is known to play a role in the maintenance of progenitor/stem cell states as well as in tumorigenesis, this mouse line will prove useful for the study of stem cell biology and cancer. Description (Set) Proposed Use (Set) In principle, the TNR1 transgenic line can be used to isolate live cells containing endogenous Notch activity from any part of the embryo or adult. Because the Notch pathway is thought to inhibit differentiation and maintain progenitor/stem cell states, this line may be useful for isolating and characterizing stem cells from various tissues. The isolation and manipulation of stem cells has commercial potential in that it may facilitate the development of cell replacement therapies to treat tissue damaged by trauma or degenerative disorders. The study of purified or enriched populations of cells defined by the common signaling event of Notch pathway activation will also permit the analysis of gene expression in these cells and may facilitate the identification of molecular markers that distinguish stem cells and other progenitor subtypes from one another.
Gaiano, Nicholas Roger
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