RESUMEN
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.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Enfermedad del Almacenamiento de Glucógeno Tipo V/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Animales , Aspartato Aminotransferasas/sangre , Calcio/sangre , Creatina Quinasa/sangre , Modelos Animales de Enfermedad , Esquema de Medicación , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Enfermedad del Almacenamiento de Glucógeno Tipo V/veterinaria , Ácido Láctico/metabolismo , Locomoción/efectos de los fármacos , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/enzimología , Fosforilasas/metabolismo , Ovinos , Factores de TiempoRESUMEN
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.
Asunto(s)
Enfermedades de los Bovinos/genética , Enfermedad del Almacenamiento de Glucógeno Tipo II/veterinaria , Enfermedad del Almacenamiento de Glucógeno Tipo V/veterinaria , Alelos , Animales , Cruzamiento , Bovinos , República Checa , Exones , Femenino , Genotipo , Glucano 1,4-alfa-Glucosidasa/deficiencia , Glucano 1,4-alfa-Glucosidasa/genética , Glucógeno Fosforilasa de Forma Muscular/deficiencia , Glucógeno Fosforilasa de Forma Muscular/genética , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Masculino , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/veterinaria , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
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.
Asunto(s)
Enfermedades de los Bovinos/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/veterinaria , Enfermedades de los Caballos/genética , Parálisis Periódica Hiperpotasémica/veterinaria , Polimorfismo de Longitud del Fragmento de Restricción , Protoporfiria Eritropoyética/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/diagnóstico , Enfermedades de los Bovinos/enzimología , ADN/química , ADN/genética , Femenino , Ferroquelatasa/genética , Glucógeno Fosforilasa de Forma Muscular/deficiencia , Glucógeno Fosforilasa de Forma Muscular/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Enfermedades de los Caballos/diagnóstico , Caballos , Masculino , Parálisis Periódica Hiperpotasémica/diagnóstico , Parálisis Periódica Hiperpotasémica/genética , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/veterinaria , Protoporfiria Eritropoyética/diagnóstico , Protoporfiria Eritropoyética/genética , Canales de Sodio/genéticaRESUMEN
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.