Expression of BRI-amyloid beta peptide fusion proteins: a novel method for specific high-level expression of amyloid beta peptides.
In order to develop transgenic animal models that selectively overexpress various Abeta peptides, we have developed a novel expression system that selectively expresses Abeta40 or Abeta42 in the secretory pathway. This system utilizes fusion constructs in which the sequence encoding the 23-amino-acid ABri peptide at the carboxyl terminus of the 266-amino-acid type 2 transmembrane protein BRI is replaced with a sequence encoding either Abeta40 or Abeta42. Constitutive processing of the resultant BRI-Abeta fusion proteins in transfected cells results in high-level expression and secretion of the encoded Abeta peptide. Significantly, expression of Abeta42 from the BRI-Abeta42 construct resulted in no increase in secreted Abeta40, suggesting that the majority of Abeta42 is not trimmed by carboxypeptidase to Abeta40 in the secretory pathway.
Lewis
P A
PA
Department of Neuroscience and Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Piper
S
S
Baker
M
M
Onstead
L
L
Murphy
M P
MP
Hardy
J
J
Wang
R
R
McGowan
E
E
Golde
T E
TE
D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid; D016229:Amyloid beta-Peptides; C120083:ITM2B protein, human; C492300:Itm2b protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins