Worm AD Model
(Click on the images for more information.)
Most of our work has employed transgenic animals that contain a chimeric unc-54/beta 1-42 minigene.
This construct produces muscle-specific expression of the human beta-amyloid peptide in the transgenic animals.
Expression of this peptide leads to amyloid deposits similar to those observed in the human brain.
Animals expressing the beta-amyloid peptide are unhealthy and show a progressive paralysis.
To investigate the relationships between the primary sequence of the beta peptide, the formation of beta-amyloid deposits, and cellular toxicity, we have generated a series of transgenic worms expressing single amino acid variants of the beta peptide.
We have also generated a novel single chain dimer construct.
As we have recently reported the met35cys and single chain dimer variants show a dramatic reduction in thioflavin S-reactive (amyloid) deposits, despite expressing appropriate levels of the human peptide.
Our current work is focusing on the characterization of mutations that suppress the paralysis observed in amyloid worms, and examining the effect of amyloid expression on global gene expression using DNA microarray analysis.

CL4176 transgenic animals, containing an
inducible muscle-specific beta peptide transgene, 24 hrs 
after induction of transgene by temperature shift.  Note 
movement is restricted to head region.  Click on 
image to see movement (download may take a few 
minutes).  Compare to the image below.


CL1175 control transgenic animals, 24 hours after 
temperature shift.   Note wild type movement.  
Click on image to see movement (download may 
take a few minutes).

 

 


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