Scientists in Spain have developed mice with a disorder that closely resembles the human metabolic muscle disorder known as McArdle disease (also called phosphorylase deficiency, myophosphorylase deficiency and glycogenosis type 5). The mice are expected to speed testing of treatments for this disorder.
The laboratory-developed mice have a mutation in both copies of the gene for myophosphorylase, an enzyme that breaks down a carbohydrate called glycogen that cells use to produce energy. (Mice and humans have two copies of most genes in each cell.)
The myophosphorylase gene mutation — known as R50X— inserted into these mice is one that commonly causes McArdle disease in humans. Like people with McArdle disease, the mice have only the mutated myophosphorylase genes; they lack normal myophosphorylase genes.
The mutation renders muscle fibers incapable of producing a functional myophosphorylase enzyme and therefore limits their capacity to derive energy from carbohydrates.
The mice showed behavioral, structural and biochemical signs of McArdle disease. These included exercise intolerance, accumulation of glycogen in their muscles, elevated levels of the creatine kinase enzyme in the blood (an indicator of muscle damage), and excretion of the myoglobin protein in the urine after exercise (another indicator of muscle damage).
Although mouse models are not perfect replicas of a human disease, they are generally considered a vital step in allowing investigators to understand a disorder and test experimental treatments.
Until now, there have been no mouse models of McArdle disease, although sheep and cattle can develop the disease naturally.
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Glycogen storage diseases — also known as glycogenoses— are a type of metabolic disorder in which cells can't break down the carbohydrate glycogen for use as energy.
Several of the metabolic muscle diseases in MDA's program are glycogenoses. These include Pompe disease (acid maltase deficiency); debrancher enzyme deficiency; lactate dehydrogenase deficiency; phosphofructokinase deficiency; phosphoglycerate kinase deficiency; phosphoglycerate mutase deficiency; and McArdle disease (phosphorylase deficiency).
The conference will include talks on living with glycogen storage disease, research updates, a panel discussion with professionals and social events.
Registration is requested by Aug. 10 and costs $50 to $75 per person. Visit the conference website for information and to register.