VANCOUVER, BC — July 6th, 2005: A scientist at the University of British Columbia’s Centre for Molecular Medicine and Therapeutics provides the first example of a human gene correcting aggressive mouse behaviour and suggests that genetic mechanisms underlying the ‘fierce’ mouse may be similar to those found in humans.
Published today in the Journal for Neuroscience, Dr. Elizabeth M. Simpson demonstrated that a human brain gene ( NR2E1 ) can prevent abnormal brain development and aggressive behaviour in mice. This work establishes a system to functionally evaluate the role of human genes in psychiatric disease.
“We now have developed a powerful paradigm that scientists can use to test, in an animal model, human genes that may be implicated in abnormal behaviour and psychiatric diseases,” says Dr. Simpson, a Canada Research Chair in Genetics and Behaviour.
Dr. Simpson uses mouse models to understand the genetic components of mental illness. In 2002, Dr. Simpson and others demonstrated that mice lacking both copies of the critical Nr2e1 gene had abnormal brain development and extreme aggressive behaviour. These mice were dubbed the ‘fierce’ mice. This earlier discovery was significant because it showed that a single gene deletion in mice could produce an extreme behaviour, regardless of environment, and in a predictable inheritance pattern.
“Our results now show that the human NR2E1 gene can replace the mouse gene resulting in a mouse with normal brain development and non aggressive behaviour. This work provides further support for the use of mouse as a model for human disease, especially in the challenging field of human brain disorders and psychiatric illness”, said Dr. Simpson. “As already seen with diabetes and cystic fibrosis, such mouse models could have significant implications for the development of new therapeutic targets for human brain disorders .”
It is still too early to know whether NR2E1 has a role in human brain disorders or aggressive behaviour. I t is often difficult to tell how much aggressive behaviour in humans can be attributed to genes versus the environment. Studying mice in a laboratory setting allows researchers to control the environment in order to examine the effects of genes and gene combinations in isolation.
For Dr. Simpson, using mice as a genetic model for human mental illness is providing significant evidence that could lead to new therapeutic targets for the treatment of such diseases.
This work was supported by Canada Foundation for Innovation, British Columbia Knowledge Development Fund, Canadian Institutes of Health Research, and the National Institutes of Health (Mental Health) USA.
Journal Reference
Title: Pathological aggression in ‘fierce’ mice corrected by human nuclear receptor 2E1 ( NR2E1 )
Author(s): Brett S. Abrahams, Melvin C.H. Kwok, Eric Trinh, Saeed Budaghzadeh, Sazzad M. Hossain and Elizabeth M. Simpson
Source: Journal of Neuroscience
The Centre for Molecular Medicine and Therapeutics (CMMT)
The Centre for Molecular Medicine and Therapeutics at the BC Children’s Hospital is a UBC research centre supported collaboratively by the Department of Medical Genetics of UBC, the British Columbia Research Institute, Merck Frosst Canada Inc., and the Government of British Columbia. Built on a 10 year history of research excellence, the CMMT is dedicated to advancing the fundamental understanding of the molecular function and structure of genes as the key to improved diagnosis, treatment and prevention of health problems in children and adults. The Centre now has 130 personnel including 6 nationally funded principal investigators and trainees, students and administrative staff.
For more information, please refer to the website at www.cmmt.ubc.ca.
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