Genetic characterization of PWS mouse - FPWR supported

Dr. Rob Nicholls has just published another study supported by FPWR. You may recall that his group developed a mouse model of PWS (and Angelman's syndrome if inherited maternally) some years back. We are currently supporting his studies to better characterize that model.
Back in the summer, I posted a summary of another FPWR-supported article from his group characterizing the metabolic problems that are present in neonatal mice with PWS including some previously unappreciated defects in pancreatic (insulin secretion) and liver function.

The current paper (available free through BioMed Central) is a very technical and detailed molecular analysis of the exact genetic disruption in this mouse. This is not something that has immediate impact for our kids, but it is a detailed understanding of how/if this mouse differs at the molecular level from human PWS is very important to understanding how the mouse can be used to study PWS.

Basically, they find that the disruption affects some sequences outside the region usually affected in human PWS, but their studies suggest that this slightly larger deletion is very similar in effect to the human type I PWS deletion. They also look at how genes in this region is normally controlled – ie, the controlling elements (promoters and enhancers) of how the genes are turned on and off in different tissues. This is important for understanding how the PWS deletion might influence expression of genes on other chromosomes, and vice versa. Coordinated expression of genes that are physically located near each other on the chromosome is a concept that has recently become better appreciated in the field of genetics, and may be important for PWS and many other genetic disorders.

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

Topics: Research

Theresa Strong


Theresa V. Strong, Ph.D., received a B.S. from Rutgers University and a Ph.D. in Medical Genetics from the University of Alabama at Birmingham (UAB). After postdoctoral studies with Dr. Francis Collins at the University of Michigan, she joined the UAB faculty, leading a research lab focused on gene therapy for cancer and directing UAB’s Vector Production Facility. Theresa is one of the founding members of FPWR and has directed FPWR’s grant program since its inception. In 2016, she transitioned to a full-time position as Director of Research Programs at FPWR. She remains an Adjunct Professor in the Department of Genetics at UAB. She and her husband Jim have four children, including a son with PWS.