title: 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.
abstract: 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 laboratories.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, Australian Neuro-muscular Research Institute, University of Western Australia, Perth, WA, Australia.
authors.forename: Yue-Bei
authors.initials: YB
authors.lastname: Luo
authors.forename: Russell D
authors.initials: RD
authors.lastname: Johnsen
authors.forename: Lisa
authors.initials: L
authors.lastname: Griffiths
authors.forename: Merrilee
authors.initials: M
authors.lastname: Needham
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Fabian
authors.forename: Sue
authors.initials: S
authors.lastname: Fletcher
authors.forename: Steve D
authors.initials: SD
authors.lastname: Wilton
authors.forename: Frank L
authors.initials: FL
authors.lastname: Mastaglia
mesh_terms: D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D052283:Creatine Kinase, MM Form / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D015854:Up-Regulation; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D052283:Creatine Kinase, MM Form
keywords: MCK-AβPP transgenic mouse; amyloid-β; inclusion body myositis; muscle histology; tubular aggregates