A Partial Transgenic Model for Alzheimer's Disease: Expression of a Fragment of the Alzheimer Amyloid Precursor cDNA
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Authors
Glendening, J. Michael
Issue Date
1992
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Alzheimer's disease is characterized by central nervous system
pathology, including the development of proteinaceous deposits consisting of
amyloid cores surrounded by neuritic degeneration (Masters et al.1985). A
principle component of these deposits is an amyloid peptide. It's amino acid
sequence is contained within a much larger precursor protein, the
Alzheimer's amyloid precursor (AAP). In vitro translation of an AAP cDNA
fragment containing the entire amyloid core protein domain, has been found
to produce a self-aggregating polypeptide (Dyrks et ale 1988). Incorporation of
a similar AAP cDNA fragment into a transgene construct, the NAN
construct, was designed to direct expression of the transgene in mouse brain
regions corresponding to those which develop characteristic Alzheimer's
disease (AD) pathology in humans. DNA and RNA analyses have shown
that the transgene has been incorporated into the genome of these mice, and
that expression is taking place. All mice analyzed herein contained a single
copy of the NAN transgene array, i.e. they were heterozygous for the array.
Regional specificity of expression has been confirmed by in situ hybridization
and is consistent with that of AD pathology. These mice are a potential
model for studying the effects of chronic AAP overexpression on brain
pathology and amyloid formation.
Description
iv, 46 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.