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

Summary 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 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 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 laboratori...
Source: International Journal of Experimental Pathology - Category: Pathology Authors: Tags: Original Article Source Type: research