Expression of BRI-amyloid β peptide fusion proteins: A novel method for specific high-level expression of amyloid β peptides

P. A. Lewis, S. Piper, M. Baker, L. Onstead, M. P. Murphy, J. Hardy, R. Wang, E. McGowan, T. E. Golde

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

In order to develop transgenic animal models that selectively overexpress various Aβ peptides, we have developed a novel expression system that selectively expresses Aβ40 or Aβ42 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 Aβ40 or Aβ42. Constitutive processing of the resultant BRI-Aβ fusion proteins in transfected cells results in high-level expression and secretion of the encoded Aβ peptide. Significantly, expression of Aβ42 from the BRI-Aβ42 construct resulted in no increase in secreted Aβ40, suggesting that the majority of Aβ42 is not trimmed by carboxypeptidase to Aβ40 in the secretory pathway.

Original languageEnglish
Pages (from-to)58-62
Number of pages5
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1537
Issue number1
DOIs
StatePublished - Jul 27 2001

Bibliographical note

Funding Information:
This work was supported by a Beeson Award from AFAR, an Ellison Medical Foundation New Scholars award and the NIH (NS39072, T.E.G.) (AG10491, R.W.) (Mayo Clinic ADRC, J.H.). BC05, BAN50, and BA27 were gifts of Takeda Industries.

Keywords

  • Alzheimer disease
  • Amyloid β protein
  • British familial dementia
  • Fusion proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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