RESUMO
McArdle disease is due to an absence of the enzyme muscle glycogen phosphorylase and results in significant physical impairment in humans. We hypothesised that sodium valproate, an HDAC inhibitor, might have the ability to up-regulate the enzyme. We treated McArdle sheep with sodium valproate given enterically at 20-60 mg/kg body wt. Compared with untreated control animals, there was increased expression of phosphorylase in muscle fibres. The response was dose dependent and reached a maximum 2 hours after the application and increased with repeated applications. Improvement in mobility could not be demonstrated. These findings suggest that sodium valproate is a potential therapeutic treatment for McArdle disease.
Assuntos
Inibidores Enzimáticos/uso terapêutico , Doença de Depósito de Glicogênio Tipo V/tratamento farmacológico , Ácido Valproico/uso terapêutico , Animais , Aspartato Aminotransferases/sangue , Cálcio/sangue , Creatina Quinase/sangue , Modelos Animais de Doenças , Esquema de Medicação , Doença de Depósito de Glicogênio Tipo V/genética , Doença de Depósito de Glicogênio Tipo V/patologia , Doença de Depósito de Glicogênio Tipo V/veterinária , Ácido Láctico/metabolismo , Locomoção/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/enzimologia , Fosforilases/metabolismo , Ovinos , Fatores de TempoRESUMO
Genotyping was carried out for glycogen storage disease type II and type V in seven cattle breeds. The analysis was carried out using the polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method. In the breeds analysed [Charolais, Czech Spotted (Czech Simmental), Belgian Blue, Limousine, Blonde d'Aquitaine, Aberdeen Angus, and Beef Simmental sires reared in the Czech Republic], the recessive allele was not found in the PYGM (phosphorylase glycogen, muscle) responsible for the glycogen storage disease type V. In the same panel, the recessive allele in exon 7, exon 9 and exon 13 of the GAA (glucosidase alpha, acid), causing the glycogen storage disease type II was not found. Therefore, we have not revealed the recessives outside previous reported breeds. The knowledge of the breed-specific occurrence of inherited disorders facilitates focusing and reduces the costs of detecting the heterozygous carriers of recessive inherited disorders.
Assuntos
Doenças dos Bovinos/genética , Doença de Depósito de Glicogênio Tipo II/veterinária , Doença de Depósito de Glicogênio Tipo V/veterinária , Alelos , Animais , Cruzamento , Bovinos , República Tcheca , Éxons , Feminino , Genótipo , Glucana 1,4-alfa-Glucosidase/deficiência , Glucana 1,4-alfa-Glucosidase/genética , Glicogênio Fosforilase Muscular/deficiência , Glicogênio Fosforilase Muscular/genética , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo V/genética , Masculino , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de RestriçãoRESUMO
Improvements to restriction fragment length polymorphism (RFLP)-based genotyping assays currently used for detection of mutations responsible for bovine ferrochelatase and myophosphorylase deficiencies, and equine hyperkalemic periodic paralysis (HYPP) are described. Reports of sporadic inhibition of restriction enzyme activity suggest a critical factor in RFLP-based genotyping assays should be assurance that restriction enzymes perform to specification with every sample. The RFLP genotyping assays that use either a mismatched recognition sequence in one or both of the oligonucleotides, or incorporate a second native site within the PCR amplicon, provide the mechanism by which efficiency of restriction enzymes can be assessed with every sample. The outcome is confirmation of the activity of the discriminating enzyme regardless of genotype.
Assuntos
Doenças dos Bovinos/genética , Doença de Depósito de Glicogênio Tipo V/veterinária , Doenças dos Cavalos/genética , Paralisia Periódica Hiperpotassêmica/veterinária , Polimorfismo de Fragmento de Restrição , Protoporfiria Eritropoética/veterinária , Animais , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/enzimologia , DNA/química , DNA/genética , Feminino , Ferroquelatase/genética , Glicogênio Fosforilase Muscular/deficiência , Glicogênio Fosforilase Muscular/genética , Doença de Depósito de Glicogênio Tipo V/diagnóstico , Doença de Depósito de Glicogênio Tipo V/genética , Doenças dos Cavalos/diagnóstico , Cavalos , Masculino , Paralisia Periódica Hiperpotassêmica/diagnóstico , Paralisia Periódica Hiperpotassêmica/genética , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Protoporfiria Eritropoética/diagnóstico , Protoporfiria Eritropoética/genética , Canais de Sódio/genéticaRESUMO
Myophosphorylase deficiency in cattle is a muscle disease induced by a C-->T point mutation in codon 489 of the myophosphorylase gene, which until now has only been diagnosed in the Charolais breed. The disease seems to be inherited in an autosomal monogenic recessive manner. A calf of double muscled phenotype was suspected of suffering from myophosphorylase deficiency based on typical symptoms, i.e. brown-coloured, transparent urine, occurring after exercise; exercise intolerance; symptoms of pain; and an elevated level of plasma creatine kinase. The presence of the previously described mutation was excluded using a newly developed, improved polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure to identify easily heterozygous carriers and homozygous affected animals.
