Prader-Willi syndrome (PWS), a genetic, metabolic and behavioral disorder, is caused by paternal deficiency for human chromosome 15. Clinic presentations include infantile hypotonia, difficult feeding, mental retardation, hypogonadism and obesity. Mitochondria play a critical role in metabolism, energy production and cell death. There are now a number of PWS transgenic mouse models that have been created. We will employ a PWS-IC deletion mouse (Chamberlain et al 2004), and the Snrpn-Ube3a deletion mouse (Tsai et al.1999) models for PWS to explore potential mitochondrial dysfunctions that may be involved in the pathophysiological pathway of PWS. We will assess mitochondrial enzyme activities, measure mitochondrial secretion of H2O2 and membrane potential. We will use MITOCHIP-microarray to analyze the changes in the expression of genes. Changes in structures of mitochondria in selected tissues (brain neurons, liver and skeletal muscles) will be evaluated by electron microscopy. Our hypothesis is that mitochondria may contribute to pathogenesis of PWS. The data will open new avenues for developing novel therapeutic strategies to combat symptoms of PWS.
Differential gene expression reveals mitochondrial dysfunction in an imprinting center deletion mouse model of Prader-Willi syndrome. Yazdi PG, Su H, Ghimbovschi S, Fan W, Coskun PE, Nalbandian A, Knoblach S, Resnick JL, Hoffman E, Wallace DC, Kimonis VE. Clinical and Translational Science. 2013 Oct;6(5):347-55.
Virginia Kimonis, M.D.
University of California, Irvine