Primary over-expression of AβPP in muscle does not lead to the development of inclusion body myositis in a new lineage of the MCK-AβPP transgenic mouse.

[inclusion body myositis]

The aim of this study is to determine whether primary over-expression of AβPP in skeletal muscle results in the development of features of inclusion body myositis (IBM ) in a new lineage of the MCK-AβPP transgenic mouse . Quantitative histological , immunohistochemical and western blotting studies were performed on muscles from 3 to 18 month old transgenic and wild-type C 5 7 BL 6 /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 AβPP in transgenic mouse muscles , deposition of amyloid-β 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 AβPP in this MCK-AβPP mouse lineage did not reach the levels required for immunodetection or deposition of amyloid-β 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 .