The Tet^OS-dnMAML-GFP transgene has the Tet response element (TRE) upstream of a cDNA sequence encoding a dominant-negative mutant variant of human Mastermind-like 1 (dnMAML) fused in-frame at its C-terminus to an enhanced green fluorescent protein (EGFP). The dnMAML-GFP fusion protein [also called DNMAML1-GFP or MAML1(13-74)-GFP] interrupts transactivation/nuclear activity of all four Notch receptors by binding the Notch-CSL [CBF1/Su(H)/Lag2 protein] transcriptional complex, but does not bind the coactivators required for transcription of target genes.

Mice homozygous for the Tet^OS-dnMAML-GFP transgene are viable and fertile with no reported phenotypic abnormalities. When bred with other mice expressing tetracycline-controlled transactivator protein (tTA) or reverse tetracycline-controlled transactivator protein (rtTA), dnMAML-GFP expression in the resulting double mutant offspring can be regulated with tetracycline or its analog doxycycline (dox). When tTA or rtTA(+dox) is present, dnMAML expression blocks the transactivation/nuclear activity of all four Notch genes by binding to the Notch-CSL [CBF1/Su(H)/Lag2 protein] transcriptional complex (preventing Notch-CSL from binding its endogenous coactivator, MAML), and results in a Notch quadruple knockout in the tTA-expressing cells. GFP expression be observed by direct/native fluorescence and antibody staining/immunohistochemistry (the donating investigator did not attempt mRNA (in situ) hybridization). As designed, Tet^OS-dnMAML-GFP transgenic mice have no reported levels of dnMAML-GFP expression in the absence of tTA.

These Tet^OS-dnMAML-GFP transgenic mice allow Tet-Off/Tet-On expression of a dominant negative form of MAML, and may be may be useful for temporally-controlled, tissue-specific blockade of Notch signaling. For example, when bred to a strain expressing tTA in blood vessel endothelial cells (VE^tTA: Stock No. 013585), the resulting double mutant mice are useful for identifying Notch target genes in endothelial-to-mesenchymal transdifferentiation in cardiac development.