In situ hybridization of muscle mitochondrial mRNA in mitochondrial myopathies.
To determine whether a mitochondrial mRNA deficiency exists in mitochondrial myopathies, muscle biopsies from a patient with chronic progressive external ophthalmoplegia (CPEO) and a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) were studied using in situ hybridization. Histochemistry and immunohistochemistry were performed along with hybridization. Hybridization reactions were widely distributed over the sarcoplasm of all muscle fibers in the patient with MELAS. In the patient with CPEO, 80% of the fibers showed a marked decrease in density of autoradiographic grains. This marked decrease corresponded to the histochemical and immunohistochemical findings of a very weak staining of cytochrome c oxidase (CCO). The isotope-labeled cDNA probe used in in situ hybridization in this study complements a part of subunit I of CCO and a part of subunit II of complex I in the mitochondrial gene. Our results suggest a defect in the mRNA in this CPEO patient.
Nakamura
S
S
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Sato
T
T
Hirawake
H
H
Kobayashi
R
R
Fukuda
Y
Y
Kawamura
J
J
Ujike
H
H
Horai
S
S
D000328:Adult; D002950:Citrate (si)-Synthase / Q000032:analysis; D003579:Cytochrome Reductases / Q000032:analysis; D015342:DNA Probes; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV / Q000032:analysis; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D009097:Multienzyme Complexes / Q000032:analysis; D009132:Muscles / Q000473:pathology*; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D010088:Oxidoreductases / Q000032:analysis; D012313:RNA / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012016:Reference Values; D013385:Succinate Dehydrogenase / Q000032:analysis; D013577:Syndrome
D015342:DNA Probes; D004272:DNA, Mitochondrial; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D012313:RNA; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D003579:Cytochrome Reductases; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase