Cre-conditional expression of constitutively active Notch1 in transgenic mice

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• The Notch signaling pathway is crucial for mammalian development.
• Constitutive activation of Notch1 signaling leads to embryonic lethality, hindering research into its specific roles.

Purpose of the Study:

• To develop a conditional transgenic mouse model to investigate the function of Notch1 signaling during embryonic development.
• To bypass embryonic lethality associated with constitutive Notch1 activation.

Main Methods:

• Created transgenic mice with a floxed beta-geo/stop signal upstream of the constitutively active intracellular domain of Notch1 (IC-Notch1).
• Activated IC-Notch1 expression using Cre recombinase, coexpressed with reporter genes (GFP or hPLAP).
• Crossed IC-Notch1 mice with a general Cre deletor line (pCX-Cre) to generate double transgenic embryos.

Main Results:

• Double transgenic embryos (IC-Notch1/pCX-Cre) exhibited widespread IC-Notch1 expression and reporter activity.
• These embryos experienced embryonic lethality before 10.5 days of gestation.
• Analysis revealed growth arrest, neural tube closure defects, disorganized somites, and disrupted vasculature.

Conclusions:

• Conditional IC-Notch1 transgenic mice are a valuable tool for studying the Notch pathway.
• This model allows for tissue-specific and inducible investigation of Notch signaling roles in development using Cre-driver lines.