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

ABSTRACT

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