Journal
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
Volume 94, Issue 6, Pages 418-425Publisher
WILEY
DOI: 10.1111/iep.12048
Keywords
amyloid-beta; inclusion body myositis; MCK-A beta PP transgenic mouse; muscle histology; tubular aggregates
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Funding
- Neuromuscular Foundation of Western Australia
- China Scholarship Council-University of Western Australia
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The aim of this study is to determine whether primary over-expression of APP in skeletal muscle results in the development of features of inclusion body myositis (IBM) in a new lineage of the MCK-APP transgenic mouse. Quantitative histological, immunohistochemical and western blotting studies were performed on muscles from 3 to 18month old transgenic and wild-type C57BL6/SJL mice. Electron microscopy was also performed on muscle sections from selected animals. Although western blotting confirmed that there was over-expression of full length APP in transgenic mouse muscles, deposition of amyloid- and fibrillar amyloid could not be demonstrated histochemically or with electron microscopy. Additionally, other changes typical of IBM such as rimmed vacuoles, cytochrome C oxidase-deficient fibres, upregulation of MHC antigens, lymphocytic inflammatory infiltration and T cell fibre invasion were absent. The most prominent finding in both transgenic and wild-type animals was the presence of tubular aggregates which was age-related and largely restricted to male animals. Expression of full length APP in this MCK-APP mouse lineage did not reach the levels required for immunodetection or deposition of amyloid- as in the original transgenic strains, and was not associated with the development of pathological features of IBM. These negative results emphasise the potential pitfalls of re-deriving transgenic mouse strains in different laboratories.
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