Amyloid-β deposition transgenic mice: Possible model of inclusion body myopathy

Ken Ichiro Fukuchi, Dao Pham, Michael Hart, Ling Li, J. Russell Lindsey

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Inclusion body myopathy is a progressive muscle disorder characterized by nuclear and cytoplasmic inclusions and vacuolation of muscle fibers. Affected muscle fibers contain deposits of congophilic amyloid, amyloid-β immunoreactive filaments, and paired helical filaments, all of which are pathological hallmarks of Alzheimer's disease in brain. Accumulations of amyloid-β and its precursor are thought to play important roles in the pathogenesis of both inclusion body myopathy and Alzheimer's disease. Overexpression of mutant forms of β protein precursor in transgenic mice by neuron-specific promoters has been reported to cause amyloid deposits in the brain. Here we report that overexpression in transgenic mice of the signal plus 99-amino acid carboxyl-terminal sequences of β protein precursor, under the control of a cytomegalovirus enhancer/β-actin promoter, resulted in vacuolation and increasing accumulation of the 4-kd amyloid-β and the carboxyl-terminus in skeletal muscle fibers during aging. These deposits in transgenic muscle only rarely showed Congo red bi-refringence. Thus, overexpression of part of β protein precursor in transgenic mice led to development of some of the characteristic features of inclusion body myopathy. These mice may be a useful model of inclusion body myopathy, which shares a number of pathological markers with Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1687-1693
Number of pages7
JournalAmerican Journal of Pathology
Volume153
Issue number6
DOIs
StatePublished - Dec 1998
Externally publishedYes

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