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OHRI scientist opens the door to better understanding and possibly finding future treatments for a severe form of mental retardation.

ABOUT 10 YEARS AGO, Dr. David Picketts was instrumental in discovering a gene that he found to be altered in patients with a severe form of mental retardation. The research, conducted while Dr. Picketts was a research fellow at Oxford University, was hailed as one of the most important discoveries in mental retardation. Largely reported in the popular media, the natural question at the time was "what is the next step."


Fast forward to today and Dr. Picketts, now a senior scientist at the Ottawa Hospital Research Institute (OHRI) - the research arm of the Ottawa Hospital and a major partner of the University of Ottawa Faculty of Medicine - and Associate Professor at the University of Ottawa, has successfully taken the research to the next step by developing a strain of mice with a genetic alteration in the same gene that causes the human disease.

In humans with mutations in the gene (called ATRX) the alteration has highly devastating consequences - causing severe mental retardation, delayed milestones (such as walking), verbal impediments, and a range of other physical abnormalities. The ATRX gene controls the action of many other genes throughout the body including the brain. It was found that even a minor defect in ATRX could have a devastating effect on day-to-day living.

As the lead scientist for this latest discovery, which will be published in the Journal of Clinical Investigation, Dr. Picketts has effectively developed an animal model in which the gene responsible for the ATRX syndrome is absent - opening the way to a far better understanding of how mutations lead to severe developmental defects. This model could also prove useful for understanding other forms of mental retardation and potentially, lead to treatments.

Dr Picketts' team discovered that, in the mutant mice many more neurons die during the formation of the brain wiring diagram when the ATRX gene is absent which leads to small brains and feeding problems, common features of newborn ATR-X syndrome patients. By generating this mouse model Dr. Picketts and his research team can now begin to investigate the mechanisms of how ATRX controls neurons and the generation of a proper wiring diagram in the developing brain. An intact wiring diagram is essential for learning and memory.

"Physicians and scientists have always faced significant limitations when trying to understand the role of any gene in complex diseases of the human brain," noted Dr. Picketts. "With the generation of this model we will now be able to determine the mechanisms that cause this form of mental retardation and perhaps pave the way for developing future therapeutic interventions."

"David's work is extremely important as it establishes that loss of neurons is the direct consequence of mutation in the ATRX gene and establishes for the first time an animal model," explained Dr. Michael Rudnicki, Director of the Molecular Medicine Program. "Without question, this study will allow the field to move forward and examine possible treatments for this terrible genetic disease."

This research was made possible thanks in part to a grant from the Canadian Institutes of Health Research.

To view the full manuscript on January 20th, visit

For more information, contact:

Nathalie Trepanier
Communications Manager/Gestionnaire, Communications
Tel:(613)798-5555 ext. 19691

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