Endocrine and molecular basis for Prader-Willi syndrome

Despite years of study, we do not yet know the basis of Prader-Willi syndrome (PWS), either the roles of the genes defective in PWS or the basis of the clinical features. Many people think the hypothalamus, a small brain region controlling appetite and many endocrine functions is solely responsible, yet this may not be the single cause and using a mouse model of PWS we have now identified a fetal defect in the pancreas, the organ that produces insulin and other hormones that regulate key energy sources in the body. Similarly, using our PWS mouse model, we have now identified a specific abnormality in the mitochondria, the powerhouse of cells, and that could underlie most or all of the clinical features of PWS. For example, deficient mitochondrial function could explain the hypotonia (poor muscle tone), endocrine dysfunction, and energy metabolism defects that lead to the opposite neonatal failure to thrive and childhood/adult obesity clinical consequences. In this work, we will determine the endocrine and biochemical basis of PWS. As such, our work will greatly advance the understanding of many aspects of PWS, with significant implications to understand the basis of the endocrine dysfunction in PWS and the potential for development of novel therapeutic interventions using our deletion mouse model of PWS.

Research Outcomes:

Hormonal and metabolic defects in a Prader-Willi syndrome mouse model with neonatal failure to thrive. Stefan M, Ji H, Simmons RA, Cummings DE, Ahima RS, Friedman MI, Nicholls RD.  Endocrinology. 146:4377-4385, 2005.

Genetic mapping of putative Chrna7 and Luzp2 neuronal transcriptional enhancers due to impact of a transgene-insertion and 6.8 Mb deletion in a mouse model of Prader-Willi and Angelman syndromes. Stefan M, Claiborn KC, Stasiek E, Chai JH, Ohta T, Longnecker R, Greally JM, Nicholls RD. BMC Genomics. 6:157, 2005.

Funded Year:


Awarded to:

Robert D. Nicholls, D.Phil. Professor of Genetics in Psychiatry




University of Pennsylvania

Research Outcomes:

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