title: Formation of gelsolin amyloid fibrils in the rough endoplasmic reticulum of skeletal muscle in the gelsolin mouse model of inclusion body myositis: comparative analysis to human sporadic inclusion body myositis.
abstract: Sporadic inclusion body myositis has a significant impact on the life of the elderly. Despite some similarities to other myopathies with established genetic defects, little is known about mechanisms of its development and no effective treatment is available. Therefore, there is a need for animal models that can faithfully reconstitute important aspects of this human disease. The authors recently expressed a mutant form of human gelsolin in mice under the control of a muscle-specific promoter. This induced myopathic changes reminiscent of human inclusion body myositis. In this study, immunogold labeling is used to further characterize this model. The study demonstrates a presence of gelsolin amyloid deposits within the rough endoplasmic reticulum. It further compares this mouse model to human sporadic inclusion body myositis.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center , Los Angeles, California , USA .
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Bannykh
authors.forename: William E
authors.initials: WE
authors.lastname: Balch
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Page
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism / Q000648:ultrastructure*; D000818:Animals; D001706:Biopsy; D004195:Disease Models, Animal; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D052097:Quadriceps Muscle / Q000378:metabolism / Q000648:ultrastructure*; D012189:Retrospective Studies
chemical_list: D000682:Amyloid; D018260:Gelsolin
references.citation: Am J Pathol. 1994 Jan;144(1):177-87
references.pmid: 8291607
references.citation: CSH Protoc. 2008 Jun 01;2008:pdb.prot5015
references.pmid: 21356849
references.citation: Nat Genet. 1992 Oct;2(2):157-60
references.pmid: 1338910
references.citation: Muscle Nerve. 2003 Apr;27(4):407-25
references.pmid: 12661042
references.citation: Nature. 2002 Jun 27;417(6892):949-54
references.pmid: 12068308
references.citation: Am J Pathol. 2004 Jan;164(1):1-7
references.pmid: 14695312
references.citation: Neuromuscul Disord. 2012 Jan;22(1):5-12
references.pmid: 22197426
references.citation: Ann Neurol. 1995 Nov;38(5):705-13
references.pmid: 7486861
references.citation: Curr Neurol Neurosci Rep. 2009 Jan;9(1):83-9
references.pmid: 19080758
references.citation: Ann Clin Res. 1969 Dec;1(4):314-24
references.pmid: 4313418
references.citation: EMBO J. 2001 Nov 15;20(22):6277-87
references.pmid: 11707399
references.citation: J Histochem Cytochem. 1995 Feb;43(2):115-23
references.pmid: 7529784
references.citation: J Clin Invest. 1991 Apr;87(4):1195-9
references.pmid: 1849145
references.citation: J Neuropathol Exp Neurol. 2002 Jun;61(6):565-71
references.pmid: 12071640
references.citation: Presse Med. 2011 Apr;40(4 Pt 2):e219-35
references.pmid: 21392932
references.citation: Neurology. 2000 Nov 14;55(9):1385-7
references.pmid: 11087787
references.citation: Exp Neurol. 2003 Feb;179(2):150-8
references.pmid: 12618121
references.citation: Science. 1967 Dec 15;158(3807):1453-5
references.pmid: 6058682
references.citation: Neurology. 2006 Jan 24;66(2 Suppl 1):S30-2
references.pmid: 16432142
references.citation: Neurosci Lett. 2011 Oct 10;503(3):229-33
references.pmid: 21896314
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11125-30
references.pmid: 19549824
references.citation: Am J Pathol. 2005 Aug;167(2):517-26
references.pmid: 16049336
references.citation: Neurology. 2006 Jan 24;66(2 Suppl 1):S20-9
references.pmid: 16432141
references.citation: Brain. 1989 Jun;112 ( Pt 3):727-47
references.pmid: 2543478