G.P.64 Histological, immunohistochemical and electron microscopic study of muscle in MCK-βAPP mice

Abstract The MCK-βAPP transgenic mouse, which carries the human amyloid precursor protein (APP) cDNA transgene, has been proposed as a model for sporadic inclusion body myositis (s-IBM). βAPP expression is confined to the skeletal muscles by the flanking muscle creatine kinase (MCK) gene, and provides a suitable model for investigating the downstream effects of selective over-expression of βAPP in muscle. We investigated the histological, immunohistochemical and ultrastructural changes in skeletal muscles in transgenic MCK-βAPP (tg; n  = 24) and wild-type mice (wt; n  = 22) aged 3–18 months. The only consistent change, which was observed equally in an age-dependent manner in both tg and wt male mice, was the presence of tubular aggregates in type II muscle fibres that has also been reported in other mouse strains. In contrast to a previous study of the MCK-βAPP mouse, no s-IBM related changes, such as inflammation, necrosis/regeneration, rimmed vacuoles or amyloid inclusions were observed and MHC-I antigen expression was not up-regulated, suggesting that these changes are not related to over-expression of βAPP. Although full length βAPP (fl-APP) has been confirmed on western blots, our failure to detect amyloid inclusions suggests that fl-APP may not be processed into β-amyloid, or that instead of accumulating in muscle fibres, β-amyloid may be secreted into the circulatory system. Our findings indicate that the MCK-βAPP mouse may not be an appropriate model of human s-IBM.