Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity.
We have previously described the creation and analysis of a Notch1 activity-trap mouse line, Notch1 intramembrane proteolysis-Cre6MT or N1IP::Cre(LO), that marked cells experiencing relatively high levels of Notch1 activation. Here, we report and characterize a second line with improved sensitivity (N1IP::Cre(HI)) to mark cells experiencing lower levels of Notch1 activation. This improvement was achieved by increasing transcript stability and by restoring the native carboxy terminus of Cre, resulting in a five- to tenfold increase in Cre activity. The magnitude of this effect probably impacts Cre activity in strains with carboxy-terminal Ert2 fusion. These two trap lines and the related line N1IP::Cre(ERT2) form a complementary mapping tool kit to identify changes in Notch1 activation patterns in vivo as the consequence of genetic or pharmaceutical intervention, and illustrate the variation in Notch1 signal strength from one tissue to the next and across developmental time.
SAGE Labs, St Louis, MO 63146, USA Department of Developmental Biology, Washington University, St Louis, MO 63110, USA.
Zhenyi
Z
Liu
Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Eric
E
Brunskill
Department of Developmental Biology, Washington University, St Louis, MO 63110, USA.
Scott
S
Boyle
Department of Developmental Biology, Washington University, St Louis, MO 63110, USA Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Shuang
S
Chen
Department of Developmental Biology, Washington University, St Louis, MO 63110, USA Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Mustafa
M
Turkoz
Department of Developmental Biology, Washington University, St Louis, MO 63110, USA Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA.
Yuxuan
Y
Guo
Department of Developmental Biology, Washington University, St Louis, MO 63110, USA.
Rachel
R
Grant
Department of Developmental Biology, Washington University, St Louis, MO 63110, USA Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA Raphael.Kopan@cchmc.org.
Raphael
R
Kopan
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts; D005697:Galactosides; D055879:Gene Knock-In Techniques; D007150:Immunohistochemistry; D007211:Indoles; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D005697:Galactosides; D007211:Indoles; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C045073:Cre recombinase; D019426:Integrases; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
Activity; Cre; Kidney; Neuron; Notch1