Cre-conditional expression of constitutively active Notch1 in transgenic mice.
The Notch signaling pathway plays a critical role during mammalian development. To bypass embryonic lethality associated with constitutive Notch1 signaling, we created transgenic mice with a floxed beta-geo/stop signal between a cytomegalo virus promoter and the constitutively active intracellular domain of Notch1 (IC-Notch1). IC-Notch1 is activated upon introduction of Cre recombinase and it is coexpressed with an enhanced green fluorescent protein or human placental alkaline phosphatase reporter. We created three IC-Notch1 transgenic mouse lines and crossed them to a general Cre deletor mouse line, pCX-Cre. The double transgenic IC-Notch1/pCX-Cre embryos have widespread expression of IC-Notch1 and reporters and die before 10.5 days of gestation. Morphological and histological analysis of the double transgenic embryos indicated growth arrest and various developmental defects, including lack of neural tube closure, disorganized somites, and disrupted vasculature. The conditional IC-Notch1 expressing transgenic mice provide a unique tool to investigate the Notch pathway using tissue-specific Cre mice and inducible Cre systems.
Liu
Ju
J
Molecular and Cellular Biology Division, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Lobe
Corrinne G
CG
D000469:Alkaline Phosphatase; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D009420:Nervous System / Q000196:embryology; D011401:Promoter Regions, Genetic; D051881:Receptor, Notch1 / Q000235:genetics*; D015398:Signal Transduction; D019170:Somites / Q000166:cytology / Q000378:metabolism
D017931:DNA Primers; D058851:GPI-Linked Proteins; D007527:Isoenzymes; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental