Home > Science > New SHANK3 model animal

New SHANK3 model animal

In a comprehensive set of studies reported on Sunday in Nature, scientists have recreated several features of autism in a mouse by inactivating or “knocking out” the SHANK3 gene. The SHANK3 mice have obsessive behaviors and social avoidance which are two of the three features that autism spectrum disorders.

Mice tend to be curious of newcomers.  However, the SHANK3 knockout mouse  avoids new mice, repeatedly choosing an isolated enclosure away from the strangers.  The obsessive behavior is manifest as over-grooming.  A typical mouse will groom itself to clean its fur, but the SHANK3 knockout mouse continues this behavior obsessively, resulting in large furless swaths of skin on its back.

The SHANK3 gene encodes a protein that helps stabilize synapses between neurons.   The authors showed that mice lacking this protein have less effective synapses in a part of their brains that is known to be involved habit formation and decision making, called the striatum.  The involvement of the striatum is important because it is a hub that is very heavily connected with other parts brain through looping circuits.

The research team also found that neurons in the striatum are larger, with more branches, possibly as way of adding more synapses to compensate for the fact that individually each synapse is less effective.  The team found that this region of the brain was larger in the knockout mouse, which mirrors a finding that has been reported in the autism literature in humans.

“Having an animal model that can teach us more about how a specific gene mutation is correlated with behavior is critically important to our understanding of the overall biology of autism,” said Andy Shih, vice president of scientific affairs at the nonprofit Autism Speaks.  By understanding more about the Shank3 pathway, we will be able to identify new medicines that can help individuals with autism by supporting more effective synapse function.

Read more about the findings of Dr. Guoping Feng and his colleagues from MIT and Duke and follow the conversation on this topic on a recent blog from a meeting about Phelan-McDermid Syndrome, which involves mutations of SHANK3.

  1. David ferrandino
    March 23, 2011 at 11:13 am

    A cure, prevention or a maintainer. I take it

  2. Katie Wright
    March 23, 2011 at 3:39 pm

    Isn’t this what Mady Hornig did 10 years ago ?

    No one in the mainstream research community has acknowledged her pioneering work on mouse models. Most importantly, Hornig’s mouse models illustrated how adjuvants can cause brain damage and ASD like regressions.

    These are triggers we can do something about now rather than 20 yrs into the future.

  3. Richard Fauth
    March 23, 2011 at 8:07 pm

    Good! Thanks for the citation of her work. I will be reading it. I am not sure why you believe that no one in the “mainstream research community” took her serious though. I also do not get the 20 year statement. There are trials now using therapuetics for both Fragile x syndrome as well as Retts syndrome. The importance of this paper is that it removed the roadblock to trials for therepeutics being investigated for Phelan Mcdermid sydrome and autism caused by shank3 mutations by breeding mice that completely knockout all of the shank 3 gene. Moreover it demonstrated even more effectively the phenotypes seen in affected children with shank 3 issues.

    I have taken the liberty of copying the abstract from the latest from study i found form the dozens listed for Mady Hornig:

    Microbiology and Immunology of Autism Spectrum Disorders
    Gregory Bock Organizer, Jamie Goode
    W. Ian Lipkin, Mady HornigPublished Online: 7 OCT 2008

    Both genetic and environmental factors are likely to contribute to the pathogenesis of neurodevelopmental disorders. Even in heritable disorders of high penetrance, variability in timing of onset or severity of disease indicate a role for modifying principles. Investigation in animal models of the consequences of interactions between host response genes and microbes, toxins, and other environmental agents in a temporal context may elucidate the pathophysiology of a wide spectrum of chronic diseases. Here we review
    the evidence that infectious and immune factors may contribute to the pathogenesis of neurodevelopmental disorders, describe an animal model of neurodevelopmentaldisorders based upon viral infection, identify processes by which neural circuitry may be compromised, and outline plans for translational research in animal models and prospective human birth cohorts.

    Additionally i am copying the abstract from a recent Study concerning Shank 3 mutations and autism. This time from Japenese researchers. This adds to studies from German, French, Italian, Canadian and American researchers identifying Shank 3 Mutations as associated to Autism spectrum Disorders:

    Psychiatric Genetics:
    doi: 10.1097/YPG.0b013e328341e069
    Brief report: PDF Only
    Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development

    Published Ahead-of-PrintAbstractThe 22q13.3 deletion syndrome is characterized by a significant delay in language development, mental retardation, hypotonia, and autistic features. Cumulative evidence has shown that haploinsufficiency of the SHANK3 gene is a major cause of the neurological symptoms of the 22q13.3 deletion syndrome. Shank3, a multidomain protein containing the SH3 and PDZ domains, is thought to play an important role in the formation and function of synapses in the developing brain. In this study, we analyzed the SHANK3 gene in 128 autistic patients with manifestations similar to those seen in the 22q13.3 deletion syndrome. The results showed a 6-amino acid deletion upstream of the SH3 domain, a missense variant (arginine to histidine at amino acid position 656) in the PDZ domain, and the insertion or deletion of a repeated 10-bp GC sequence located 9-bp downstream from the 3′ end of exon 11. None of these variants was found in 228 controls.

    (C) 2011 Lippincott Williams & Wilkins, Inc.

    I do not get why some people believe that autism research that focuses on genetics is contrary to autism research that focuses on factors in the environment. Nature and nurture are likely involved-why is there a controversy?

  4. March 24, 2011 at 6:52 am

    I hope you don’t mind me leaving my link here, but this research – and some reactions to it – prompted me to write an article.

    AUTISM: Who I Am http://nblo.gs/fNoAF

    I really think this research is interesting, but I do wonder what the effects of it will be in the real world.

  5. Sarah
    March 24, 2011 at 9:15 am

    I love animal model studies.

    Dr. Hornig is one of the researchers I site when I discuss how mainstream environment/immune system/neuropsychiatric research is.

    Unfortunately, the scientific community needs tons of corroborating researchers and articles for any research to become accepted. (Think about global warming for example. The global warming research is overwhelming, but it took years and many, many researchers/institutions.) With Autism Speaks’ guidance the research that floats our particular-science-obsessed-ASD-parent boats is becoming more and more mainstream everyday.

    So yes, Dr. Hornig is certainly a pioneer. Thankfully, there are now more and more researchers in her area.

  6. June 29, 2011 at 11:04 pm

    Interesting. It’s the way to advance and create new medicines to cure human illness

  7. June 29, 2011 at 11:05 pm

    I wonder how we can advance in medicine within a few years

  8. June 29, 2011 at 11:08 pm

    I would be very happy to find someone who gets cured of such a thing. Autism is something many people have been fighting against for a long time. It must be hard to live with something like that

  9. August 28, 2011 at 8:22 am

    I was quite impressed by this article and by how there are so many different ways of doing research that might help create a cure for autism – or at the very least help us understand it much, much better. I personally have never cared much for my biology classes in school, but this is a tremendously interesting approach to autism reserach. I was never aware of going at it from this angle, and I am truly impressed. Keep up the good work.

  10. September 8, 2011 at 5:23 pm

    how important is this research, some day we will find any disease and behavior. already come so far and I hope you have fast solutions.

  1. March 25, 2011 at 8:53 am
  2. March 25, 2011 at 8:43 pm
  3. April 8, 2011 at 11:12 am

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