Related Experiment Videos
Mice lacking both presenilin genes exhibit early embryonic patterning defects.
D B Donoviel1, A K Hadjantonakis, M Ikeda
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G-1X5. donoviel@mshri.on.ca
Genes & Development
|November 11, 1999
Summary
Presenilins (PS1 and PS2) are crucial for mammalian embryonic development and Notch signaling. Loss of both presenilins causes severe early patterning defects and embryonic lethality, revealing functional redundancy between PS1 and PS2.
Area of Science:
- Developmental Biology
- Genetics
- Neuroscience
Background:
- Presenilins (PS1 and PS2) are implicated in Notch signaling and Alzheimer's Disease pathogenesis.
- PS1-null mice exhibit perinatal lethality, suggesting potential genetic redundancy with PS2.
Purpose of the Study:
- To investigate the functional redundancy between presenilin 1 (PS1) and presenilin 2 (PS2) in mammalian development.
- To determine the role of presenilins in early embryonic patterning and Notch signaling.
Main Methods:
- Gene targeting to generate PS2-null and PS1/PS2 double-null mice.
- Phenotypic analysis of knockout embryos, including assessment of developmental defects and gene expression (Dll1, Hes-5).
Main Results:
- PS2-null mice show no obvious defects, but PS1/PS2 double-null mice exhibit embryonic lethality at E9.5.
- Double-null embryos display widespread early patterning defects, including somite segmentation, neural tube organization, and organogenesis.
- Notch pathway genes Dll1 and Hes-5 are misexpressed in double-null embryos, indicating presenilins' role in Notch signaling.
Conclusions:
- Vertebrate presenilins (PS1 and PS2) play essential, widespread roles in embryogenesis.
- There is significant functional redundancy between PS1 and PS2.
- Presenilins are critical for proper Notch signaling during vertebrate development.