Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis

The nucleic acid binding protein TDP‐43 was recently identified in normal myonuclei and in the sarcoplasm of inclusion body myositis (IBM) muscle. Here we found TDP‐43 sarcoplasmic immunoreactivity in 23% of IBM myofibers, while other reported IBM biomarkers were less frequent, with rimmed vacuoles...

Full description

Saved in:
Bibliographic Details
Published in:Muscle & nerve 2009-07, Vol.40 (1), p.19-31
Main Authors: Salajegheh, Mohammad, Pinkus, Jack L., Taylor, J.Paul, Amato, Anthony A., Nazareno, Remedios, Baloh, Robert H., Greenberg, Steven A.
Format: Article
Language:English
Subjects:
Amyloid beta-Peptides - metabolism
Biological and medical sciences
Cardiovascular system
Congo Red
Diseases of striated muscles. Neuromuscular diseases
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Humans
inclusion body myositis
Indoles
inflammatory myopathies
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Muscle Fibers, Skeletal - cytology
Myositis, Inclusion Body - metabolism
Myositis, Inclusion Body - pathology
Neurofilament Proteins - metabolism
Neurology
Oligonucleotide Array Sequence Analysis - methods
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Sarcoplasmic Reticulum - metabolism
TDP-43
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The nucleic acid binding protein TDP‐43 was recently identified in normal myonuclei and in the sarcoplasm of inclusion body myositis (IBM) muscle. Here we found TDP‐43 sarcoplasmic immunoreactivity in 23% of IBM myofibers, while other reported IBM biomarkers were less frequent, with rimmed vacuoles in 2.8%, fluorescent Congo red material in 0.57%, SMI‐31 immunoreactivity in 0.83%, and focal R1282 beta‐amyloid immunoreactivity in 0.00% of myofibers. The presence of as little as >1% of myofibers with nonnuclear sarcoplasmic TDP‐43 was highly sensitive (91%) and specific (100%) to IBM among 50 inflammatory myopathy patient samples, although some patients with hereditary inclusion body myopathies and myofibrillar myopathy also had sarcoplasmic TDP‐43. TDP‐43 mutations were sought, and none were identified. TDP‐43 could be one of many nucleic acid binding proteins that are abnormally present in IBM sarcoplasm. They could potentially interfere with the normal function of extranuclear RNAs that maintain myofiber protein production. Muscle Nerve 40: 19–31, 2009
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.21386