09-07-2007, 04:13 PM
Quote:
Autistic mice show skills similar to human cases
MUTANT mice with an autism gene display striking learning skills mirroring those seen in human "savants", new research shows.
The main abnormality seen in the genetically engineered mice was a poor ability to interact socially, a hallmark of aut-ism disorders.
But this was coupled with significantly enhanced spatial learning and memory skills. The mutants were better able than normal mice to learn and remember the location of a submerged platform.
The mice produced by scientists at Howard Hughes Medical Institute in Chevy Chase, Maryland, in the United States, have a mutant version of a gene called neuroligin-3. The same variant is found in some humans with classical autism and Asperger syndrome, a particular autistic disorder.
Neuroligin-3 produces a protein involved in the junction points that let nerve cells to "talk" to each other.
Autism in humans has also produced individuals with unusual memory gifts. So-called "savants" have performed astonishing feats of drawing from memory, the playing of intricate classical music after one listening, and complex maths calculations at speed.
Dr Thomas Sudhof, who led the research published in the online version of Science, said the "remarkable" mice offered a new tool for understanding autism.
MUTANT mice with an autism gene display striking learning skills mirroring those seen in human "savants", new research shows.
The main abnormality seen in the genetically engineered mice was a poor ability to interact socially, a hallmark of aut-ism disorders.
But this was coupled with significantly enhanced spatial learning and memory skills. The mutants were better able than normal mice to learn and remember the location of a submerged platform.
The mice produced by scientists at Howard Hughes Medical Institute in Chevy Chase, Maryland, in the United States, have a mutant version of a gene called neuroligin-3. The same variant is found in some humans with classical autism and Asperger syndrome, a particular autistic disorder.
Neuroligin-3 produces a protein involved in the junction points that let nerve cells to "talk" to each other.
Autism in humans has also produced individuals with unusual memory gifts. So-called "savants" have performed astonishing feats of drawing from memory, the playing of intricate classical music after one listening, and complex maths calculations at speed.
Dr Thomas Sudhof, who led the research published in the online version of Science, said the "remarkable" mice offered a new tool for understanding autism.
Quote:
Socially Awkward Mice Are Apt Models for Autism Research
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
September 06, 2007
Add Your Knowledge™ Additional Autism Coverage
DALLAS, Sept. 6 -- Clues into how autism spectrum disorders work may emerge from mice with a mutation that makes them socially awkward but enhances cognitive abilities. Action Points
Explain to patients who ask that the research described here was conducted only in mice, and that it is not known whether the same findings apply to people.
Explain that the genetic mutation the authors described is seen in only a small percentage of people with autism spectrum disorders.
Transgenic mice with a mutation in the gene encoding for neuroligin-3, a synaptic cellular adhesion molecule, showed both social impairment and enhanced spatial learning abilities, a mix typical of some patients with autism, Asperger's syndrome, or related conditions, reported Thomas C. Südhof, M.D., of the University of Texas Southwestern here, and colleagues.
The behavioral changes the investigators observed in the mice were accompanied by increases of inhibitory synaptic transmission but not excitatory transmission, the authors reported online in Science Express, the rapid online version of Science.
"Our data strongly support the notion that a change in the inhibitory-excitatory balance contributes to the pathogenesis of autism spectrum disorders," they wrote.
If it can be shown that the mouse model accurately mimics the pathology of autism, it would suggest the possibility of treating some forms of autism spectrum disorders with therapies that can attenuate inhibitory synaptic transmission, the investigators said.
To see whether autism may be caused by an imbalance in synaptic circuits, the authors bred mice with an R451C-substitution in the gene encoding for neuroligin-3. A related mutation in humans is associated with familial idiopathic autism.
The investigators also bred a line of neuroligin-3 knockout mice for comparison purposes. They found that both murine strains appeared to be physically normal and had normal life spans.
The genetic substitution resulted in about a 90% reduction in neurologin-3 in the forebrain, and the deletion of the gene results in complete absence of the cellular adhesion molecule. However, mice with the R451C-substitution had an increase in the strength of inhibitory synaptic impulses, whereas the knockout mice did not. There were no significant changes in excitatory synaptic transmission.
The investigators then looked at the behaviors of the animals with the gene substitution to see whether the changes in synaptic transmission translated into changes in social behavior.
They found that the R451C-substitution mice were no different from wild-type controls in the time they spent examining a new inanimate object in their cages. But when a new caged adult mouse was introduced, they showed a small but significant decrease in interaction times compared with wild-type mice.
Although the neuroligin-3 deficient mice had social deficits, they appeared to have enhanced spatial memory, taking fewer days to learn the location of the submerged platform in a swim test, and finding the platform location nearly twice as often as controls.
"This combination of electrophysiological and behavioral effects is quite remarkable," Dr. Südhof said. "It was also significant that these mice did not exhibit any other impairment of nervous system function -- there was no abnormal locomotor activity or motor coordination, for example. This was a selective change, with social impairment on the one hand, yet cognitive enhancement on the other."
The study was supported by the National Institute of Mental Health. Potential author conflicts of interest were not listed.
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
September 06, 2007
Add Your Knowledge™ Additional Autism Coverage
DALLAS, Sept. 6 -- Clues into how autism spectrum disorders work may emerge from mice with a mutation that makes them socially awkward but enhances cognitive abilities. Action Points
Explain to patients who ask that the research described here was conducted only in mice, and that it is not known whether the same findings apply to people.
Explain that the genetic mutation the authors described is seen in only a small percentage of people with autism spectrum disorders.
Transgenic mice with a mutation in the gene encoding for neuroligin-3, a synaptic cellular adhesion molecule, showed both social impairment and enhanced spatial learning abilities, a mix typical of some patients with autism, Asperger's syndrome, or related conditions, reported Thomas C. Südhof, M.D., of the University of Texas Southwestern here, and colleagues.
The behavioral changes the investigators observed in the mice were accompanied by increases of inhibitory synaptic transmission but not excitatory transmission, the authors reported online in Science Express, the rapid online version of Science.
"Our data strongly support the notion that a change in the inhibitory-excitatory balance contributes to the pathogenesis of autism spectrum disorders," they wrote.
If it can be shown that the mouse model accurately mimics the pathology of autism, it would suggest the possibility of treating some forms of autism spectrum disorders with therapies that can attenuate inhibitory synaptic transmission, the investigators said.
To see whether autism may be caused by an imbalance in synaptic circuits, the authors bred mice with an R451C-substitution in the gene encoding for neuroligin-3. A related mutation in humans is associated with familial idiopathic autism.
The investigators also bred a line of neuroligin-3 knockout mice for comparison purposes. They found that both murine strains appeared to be physically normal and had normal life spans.
The genetic substitution resulted in about a 90% reduction in neurologin-3 in the forebrain, and the deletion of the gene results in complete absence of the cellular adhesion molecule. However, mice with the R451C-substitution had an increase in the strength of inhibitory synaptic impulses, whereas the knockout mice did not. There were no significant changes in excitatory synaptic transmission.
The investigators then looked at the behaviors of the animals with the gene substitution to see whether the changes in synaptic transmission translated into changes in social behavior.
They found that the R451C-substitution mice were no different from wild-type controls in the time they spent examining a new inanimate object in their cages. But when a new caged adult mouse was introduced, they showed a small but significant decrease in interaction times compared with wild-type mice.
Although the neuroligin-3 deficient mice had social deficits, they appeared to have enhanced spatial memory, taking fewer days to learn the location of the submerged platform in a swim test, and finding the platform location nearly twice as often as controls.
"This combination of electrophysiological and behavioral effects is quite remarkable," Dr. Südhof said. "It was also significant that these mice did not exhibit any other impairment of nervous system function -- there was no abnormal locomotor activity or motor coordination, for example. This was a selective change, with social impairment on the one hand, yet cognitive enhancement on the other."
The study was supported by the National Institute of Mental Health. Potential author conflicts of interest were not listed.
This reminds me of The Secret of NIMH. The study was even supported by NIMH. Did any of you see this animated movie?
