A Partial Transgenic Model for Alzheimer's Disease: Expression of a Fragment of the Alzheimer Amyloid Precursor cDNA
Glendening, J. Michael
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.
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