Transthyretin Val122Ile, accumulated Abeta, and inclusion-body myositis aspects in cultured muscle.
Cultured muscle fibers (CMF) from a patient with inclusion-body myositis (IBM) and cardiac amyloidosis associated with the transthyretin (TTR) Val122Ile mutation contained aspects of the IBM phenotype: vacuolation, congophilic inclusions, and clusters of immunocolocalizing amyloid beta-peptide (Abeta) and TTR accumulations. These abnormalities are never present in normal human CMF. These perturbations were greatly increased after Abeta precursor protein gene transfer. The TTR mutation may be a genetic predisposition factor for the patient's IBM.
Askanas
Valerie
V
USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA. askanas@hsc.usc.edu
Engel
W King
WK
McFerrin
Janis
J
Vattemi
Gaetano
G
D000368:Aged; D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D016923:Cell Death; D002478:Cells, Cultured / Q000737:chemistry; D004396:Coloring Agents; D003224:Congo Red; D018076:DNA, Complementary / Q000235:genetics; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000648:ultrastructure; D008297:Male; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D020125:Mutation, Missense; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011228:Prealbumin / Q000032:analysis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014617:Vacuoles / Q000648:ultrastructure
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004396:Coloring Agents; D018076:DNA, Complementary; D011228:Prealbumin; D011993:Recombinant Fusion Proteins; D003224:Congo Red