title: Transcriptional Signature of an Altered Purine Metabolism in the Skeletal Muscle of a Huntington's Disease Mouse Model.
abstract: Huntington's disease (HD) is a fatal neurodegenerative disorder, caused by a polyglutamine expansion in the huntingtin protein (HTT). HD has a peripheral component to its pathology: skeletal muscles are severely affected, leading to atrophy, and malfunction in both pre-clinical and clinical settings. We previously used two symptomatic HD mouse models to demonstrate the impairment of the contractile characteristics of the hind limb muscles, which was accompanied by a significant loss of function of motor units. The mice displayed a significant reduction in muscle force, likely because of deteriorations in energy metabolism, decreased oxidation, and altered purine metabolism. There is growing evidence suggesting that HD-related skeletal muscle malfunction might be partially or completely independent of CNS degeneration. The pathology might arise from mutant HTT within muscle (loss or gain of function). Hence, it is vital to identify novel peripheral biomarkers that will reflect HD skeletal muscle atrophy. These will be important for upcoming clinical trials that may target HD peripherally. In order to identify potential biomarkers that might reflect muscle metabolic changes, we used qPCR to validate key gene transcripts in different skeletal muscle types. Consequently, we report a number of transcript alterations that are linked to HD muscle pathology.
authors.affiliation: Department of Life Sciences, Imperial College LondonLondon, UK; Department of Epidemiology of Rare Diseases and Neuroepidemiology, Poznan University of Medical SciencesPoznan, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Mielcarek
authors.affiliation: Department of Biochemistry, Medical University of Gdańsk Gdańsk, Poland.
authors.forename: Ryszard T
authors.initials: RT
authors.lastname: Smolenski
authors.affiliation: Department of Life Sciences, Imperial College London London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Isalan
keywords: Huntington's disease; biomarkers; mouse models; purine metabolism; skeletal muscle atrophy; transcriptional deregulation