Of Mice, Synapses, and Autism
December 9, 2007 by Kristina Chew, PhD
Filed under Health
Scientists at the University of Texas Southwestern Medical Center have developed the first-ever genetic animal model of autism by introducing a genetic mutation in mice. Under Thomas Südhof, M.D., professor and chairman of neuroscience at UT Southwestern, the researchers replaced a normal mouse neurologin-3 gene with a mutated neuroligin-3 gene associated with autism in humans.Neurologins ensure that signal transitions between nerve cells function and are “expressed on the surface of the postsynaptic neuron” and bind to neurexins, which are proteins on the presynaptic neuron. It is thought that neuroligins and neurexins together “play key roles in the forming and functioning of synapses.” According to the September 8th Science Daily:
Dr. [Craig] Powell studied the genetically altered mice and found that, when examined in behavioral tests that may reflect key signs of autism, they showed decreased social interaction with other mice; other traits, such as anxiety, coordination and pain sensitivity, were unaffected. These social interaction deficits, Dr. Powell says, are hallmark features of human autism. In addition, the mice showed enhanced spatial learning abilities, which may resemble the enhanced cognitive abilities in autistic savants (people who have a severe developmental or mental handicap as well as extraordinary mental abilities).
“These findings could be especially helpful in identifying novel treatment approaches. We already know that inhibitory chemical synaptic transmission from one neuron to the next is increased in this mouse model. Now we can test drugs that decrease this effect directly in the mice and ask whether this reverses their social interaction deficits,” Dr. Powell says. “For now, the mainstay of autism treatment is still behavioral therapy. The earlier we can get patients involved with behavioral interventions, the better off people with autism will be.” Dr. Powell adds that the model gives researchers insight into mouse brains which share important parallels with brains of living humans, which can only be studied in limited ways with the use of new brain imaging tools.
Interesting that the two “autistic traits” that are noted in the mice are “social interaction deficits” and also “enhanced spatial learning” and “enhanced cognitive” abilities, and that these are related to synapses in the brain. In watching my son Charlie grow up, these are the features I particularly remark in him, more than in his language and speech, whether or not he makes eye contact, or any gastrointestinal issues. I ask him to “put the plate in front of the microwave” and he pauses, blinks, pulls his lips, and picks up the plate and slides it towards me. I repeat the instruction, and the plate is rapped against the door of the microwave, the microwave door is opened, the plate is pushed towards the sink—-Charlie all the while so tremendously patient to try to do something with that I have asked. It’s evident that he is hearing me and that his mind is working at what I have said; coordinating the sounds of words and his thoughts and the motions of his arm and fingers: It’s in connecting all of these that something that gets garbled, that the connections don’t connect. (Not that a genetically altered mouse is going to have to orchestrate that complex of motions and thoughts.)
This kind of thing drives me crazy. I won’t even address the mouse-to-human jump. What if autism is a) radically heterogeneous and/or b) not really a problem of some inate social defecit? Researchers tend to work backwards from an accepted notion of what autism is and then try to produce this effect in a mouse, say. Donna Williams, Tito M., Lucy Blackman, Jamie Burke, Sue Rubin–none of these people buy the social defecit model. Rather, they talk about a range of sensory problems, along with anxiety, that make sociality difficult–difficult but not impossible. There’s a big difference between what the researchers presume and what Autists are telling us. What if a researcher–think of Morton Gernsbacher–refused to begin with the cultural stereotype of autism but, rather, sought to better understand what’s really going on in autism. The researcher might find, as Gernsbacher and Mottron and Dawson did, that there isn’t the proclaimed intelligence defecit that the experts had decreed. Changing the IQ test made all the difference in the Gernsbacher & Motron & and Dawson example. Finally, I think it’s a big mistake to assume that increased spatial perception must come AT THE EXPENSE of other abilities. Again, this isn’t necessarily true. Just ask the Auties I mention above.
Ralph Savarese, PhD
Thanks so much for this—–it does seem that researchers start presuming they know what autism is and just to “knock out” in the genes of a mouse. I was curious that they used the phrase “human autism.”
Mr. Saverese
The researchers involved in the study did not suggest that a study involving mice is final and conclusive , far from it. But your superficial rejection of serious research is interesting. Mottron, Gernsbacher and Dawson are engaged in research to substantiate their ideological views about autism which you share. They offer little research outside that limited focus.
Ask the auties? OK, I will ask my son, who has Autism Disorder, who speaks at a very rudimentary, concrete level and who has a limited understanding of the world. What will my son the “autie” say? Of course he has Autism Disorder, actual Autism Disorder, perhaps your were referring to someone on the spectrum of pervasive developmental disorders diagnosed with Aspergers or some other similar but distinct condition?
By the way, since you and Ms Chew are very word sensitive, highly educated Ph D’s with literary backgrounds I have to say, as the father of an autistic 12 year old boy with Autism Disorder, that I find the term “Autie” offensive, denigrating and stereotypical.
We’ll (I, at least!) will be glad to start deconstructing the term “autie” for you; it might further be helpful to consider some works of autiebiography.
Hi Ralph, in my son’s case I don’t think it’s mostly a sensory issue that makes it harder for him to participate or understand social situations and rules. I think it is more a matter of not being aware of other people’s social expectations and “not seeing the point”, or the use of behaving as expected/demanded. He is affectionate and loves to socialize, but he does it in his own terms, or in the ways he had to be taught (greetings, taking turns in games, answering to questions, etc).
I agree that autism is very heterogenous. While for many kids the anxiety and sensory problems are the main struggles, I see my autistic child as a very easy-going person whose main challenge is following instructions that do not agree with his own agenda; and of course learning language and social rules has been really difficult for him. But I can take him anywhere that’s loud, crowded, with blinking lights, he won’t care… He doesn’t mind the feel of different clothes, or grass, sand, mud, bark or water; he doesn’t need a schedule or previous warnings of where we’re going, he pretty much goes with the flow.
I also think that the mice study should not be dismissed, most research cannot encompass the total range of causes and symptoms of autism. Current knowldedge says it involves multiple genes, and those scientists are manipulating only one of the genes that might be associated with the disorder. The fact that the social skills and space/visual skills are affected by that same gene is a very insteresting discovery.
Charlie too does not seem bothered by loud noises—it’s the high-pitched ones (sometimes my voice; have to watch it) that can irk him.
The latest spin on these findings is that autism can be “induced” in mice.
I too have problems with folks saying they have modeled human autism in mice, as they haven’t even defined what human autism is completely yet, or we would already have someone’s disgusting genetic tests already approved and verified.
/start sarcasm
I think it is also sensationalising themselves in their own mind to say that this is the first ever model. We have been reading about autistic mice for years, just because they weren’t nlgn3 knockouts didn’t mean they were inferior/lacking of the love and support all the other AutMice have gotten.
I think we need genetically engineered mice testing for curebiesm and politicians and lawyers too, let’s not diskriminate too much.
/end sarcasm
Have any of you heard of using the gene deletion in William’s syndrome as a model for autism in mice?
Synapse disruptions have also been observed in mice prenatally exposed to the anti-convulsant Sodium Valproate, one of the few known environmental causes of autism and other developmental disorders by interrupting normal brain development and synapse connections.
hattp://cercor.oxfordjournals.org/cgi/content/abstract/bhm117v1
Th original article makes the genetic claim based on two sisters from the same family that were found to have the neurologin anomaly….. Out of 3,000 persons whose DNA is in the AGRE data base. The anomaly was not found in other large samples of multiple incidence familiesb but has been found in mentally retarded and schizophrenic people.
The congenital anti-convulsant syndrome associated with autism has been accepted as conclusive by both genetic researchers and environmental researchers.
Synapse disruptions have also been observed in mice prenatally exposed to the anti-convulsant Sodium Valproate, one of the few known environmental causes of autism and other developmental disorders by interrupting normal brain development and synapse connections.
http://cercor.oxfordjournals.org/cgi/content/abstract/bhm117v1
Th original article makes the genetic claim based on two sisters from the same family that were found to have the neurologin anomaly….. Out of 3,000 persons whose DNA is in the AGRE data base. The anomaly was not found in other large samples of multiple incidence familiesb but has been found in mentally retarded and schizophrenic people.
The congenital anti-convulsant syndrome associated with autism has been accepted as conclusive by both genetic researchers and environmental researchers.
Ah, Texas. I live in a state where an amazing amount of funding is being thrown at controlling the undesirable behaviors of, or simply eradicating, those like me, but the state organizations that are supposed to be their to help me won’t help with legal matters, suggesting I get a lawyer on my own, the local ASA chapter ignores my email, and the assistance counselor just stopped talking to me completely.