Research on molecular mechanisms ofMcArdle's disease (muscle glycogen phosphorylase deficiency)

Lack of muscle glycogen phosphorylase activity leads to McArdle's disease, a rare metabolic myopathy. To investigate its molecular basis at the nucleic acid level, we isolated muscle phosphorylase cDNA clones from a human cDNA library in Escherichia coli plasmid pBR 322. Subcloning of one insertion of M13 bacteriophage permitted its definite identification by sequencing. Northern blot experiments revealed one specific messenger RNA of 3.4 kilobases found uniquely in tissues expressing muscle phosphorylase.We show that McArdle's disease exhibits a molecular heterogeneity at the messenger RNA level. In eight unrelated cases of McArdle's disease in which no inactive proteins had been detected, we assayed muscle biopsies for phosphorylase mRNA by Northern blotting. In five cases, no muscle phosphorylase mRNA could be detected, while in three other cases, normal length mRNA was present in lower amounts.Moreover, Southern blot analysis of DNA isolated from white blood cells in four McArdle patients revealed no major deletion or rearrangements of the phosphorylase gene as compared with controls.

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“…4). In five patients (2,5,6,9, and 10) no specific phosphorylase mRNA could be seen, whereas aldolase A mRNA was present.…”

Section: Resultsmentioning

confidence: 99%

Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency). RNA and DNA analysis.

Gautron¹,

Daegelen²,

Mennecier³

et al. 1987

J. Clin. Invest.

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“…Daegelen-Proux et al [ 1 ] described the presence of an inactive protein in muscle biopsy extracts from patients with myophosphorylase deficiency by using two-dimen sional electrophoresis and immunoaffinity microchro matography.…”

Section: Discussionmentioning

confidence: 99%

Histochemical and Biochemical Studies in a Patient with Myophosphorylase Deficiency

Tachi

Sasaki²,

Tachi³

et al. 1990

Eur Neurol

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The present report describes the histochemical and biochemical findings of biopsied muscles in a 26-year-old male with myophosphorylase deficiency. Histochemical analysis of the first biopsy specimen revealed that the phosphorylase activity was absent, corresponding to an absent band at 94,000 Da on the basis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Histochemically the second biopsy specimen showed a partial phosphorylase activity of type 2B fibers, corresponding to a weakly staining band at 94,000 Da on the basis of SDS-PAGE. The present study supports the hypothesis that myophosphorylase deficiency is essentially a single gene disorder, characterized by absence or marked reduction of the myophosphorylase protein.

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“…Molecular studies of myophosphorylase deficiency revealed that in most cases the protein is absent and the mRNA is missing or greatly reduced (4)(5)(6), in some patients there is a normal amount of either full-length or shorter mRNA, and in a few patients an inactive protein of normal or reduced size can be shown by immunoreaction with anti-M-GP antiserum (5)(6)(7)(8)(9). In human tissues there are three different isoforms ofglycogen phosphorylase (GP) ( 10), which are encoded by three separate genes (1 1-13).…”

Section: Introductionmentioning

confidence: 99%

Expression of muscle-type phosphorylase in innervated and aneural cultured muscle of patients with myophosphorylase deficiency.

Martinuzzi¹,

Vergani²,

Carrozzo³

et al. 1993

J. Clin. Invest.

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Patients with McArdle's myopathy lack muscle glycogen phosphorylase (M-GP) activity. Regenerating and cultured muscle of patients with McArdle's myopathy presents a glycogen phosphorylase (GP) activity, but it is not firmly established whether M-GP or non-M-GP isoforms are expressed.We have cultured myoblasts from biopsy specimen of five patients with McArdle's myopathy. Skeletal muscle was cultured aneurally or was innervated by coculture with fetal rat spinal cord explants. In the patients' muscle biopsies and in their cultured innervated and aneural muscle we studied total GP activity, isoenzymatic pattern, reactivity with anti-M-GP antiserum, and presence of M-GP mRNA. There was no detectable enzymatic activity, no immunoreactivity with anti-M-GP antiserum, and no M-GP mRNA in the muscle biopsy of all patients. GP activity, M-GP isozyme, and anti-M-GP antiserum reactivity were present in patients' aneural cultures, increased after innervation, and were undistinguishable from control. M-GP mRNA was demonstrated in both aneural and innervated cultures of patients and control by primer extension and PCR amplification of total RNA. Our studies indicate that the M-GP gene is normally transcribed and translated in cultured muscle of patients with myophosphorylase deficiency. (J.

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Research on molecular mechanisms ofMcArdle's disease (muscle glycogen phosphorylase deficiency)

Cited by 11 publications

References 16 publications

Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency). RNA and DNA analysis.

Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency). RNA and DNA analysis.

Histochemical and Biochemical Studies in a Patient with Myophosphorylase Deficiency

Expression of muscle-type phosphorylase in innervated and aneural cultured muscle of patients with myophosphorylase deficiency.

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