Neuroscience

Genetics and Aggressive Behavior in a Mouse Model

From The Globe and Mail:

Rampaging mice made more human
By CAROLYN ABRAHAM
Wednesday, July 6, 2005 Updated at 8:57 AM EDT
From Wednesday's Globe and Mail

A breakthrough experiment has used a human gene to turn vicious mice into very gentle creatures -- holding out the prospect of doing similarly sweet things to violent people.

Scientists at the University of British Columbia's Centre for Molecular Medicine and Therapeutics created a strain of extremely vicious lab mice three years ago after accidentally deleting a gene that affects brain development.

The mutant mice were so aggressive they killed their mates, chewed their siblings' tails and even attacked their lab handlers.

The unanswered question was whether the human form of the gene also plays a role in aggression in people. The new research now suggests that it does.

By giving mutant mice embryos the human version of the gene they were missing, the UBC team found the nasty rodents grew into a rather nice strain instead.

As such, the experiment raises the possibility of designing a gene therapy to counter aggression -- as well as the eerie spectre of enhancing it.

More immediately, it means mice can act as models to study human genes involved in abnormal behaviour and psychiatric disorders.

[ ... Read the full article ... ]~
From the UBC press release:

Human Gene Corrects Pathological Aggression in Mice
Mouse model opens new door to testing genetic causes of mental illnesses

VANCOUVER, BC – July 6th, 2005: Dr. Elizabeth M. Simpson, a CMMT investigator at the BC Research Institute, 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.“

-
Anthony H. Risser | neuroscience | neuropsychology | brain

- D1 Receptor Knock-out Mice Say, "no Cocaine For Us!"
"However, we'll still take plenty of food and opioid agonists!" Unlike mice with the dopamine D2 receptor "knocked out," D1 receptor-deficient mice will no longer self-administer cocaine: Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob...

- Neuropsychology Abstract Of The Day: Alzheimer's Disease
Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model J Neurochem. 2011 Sep; 118(5): 928-38 Authors: Fabbro S, Schaller K, Seeds NW Abstract...

- The Brain That Squeaked
From today's New York TImes: Atlas Squeaked: A Complete Map of the Brain of a Mouse By NICHOLAS WADE Published: September 26, 2006 The New York Times Scientists have gained a new window for peering into the brain, courtesy of a $41 million project...

- Knockout Mice Are The Bomb!
From an NIH press release from earlier today: NIH Launches Knockout Mouse Project Genome-Wide Public Resource Will Provide New Mouse Models for Understanding Human Disease The National Institutes of Health (NIH) today awarded a set...

- Evo Devo Explained
A book review in the Oct. 24, 2005 issue of the New Yorker by H. Allen Orr explains a bit about “evo devo” (evolutionary developmental biology), and finally clarifies for me what “ontogeny recapitulates phylogeny” means. Last things first: the...

Neuroscience