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The Importance of Model Systems

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Animal models of autism, including cell based models, have received criticism because autism is a uniquely human condition so there is no value in studying it in a model like a mouse or a cell. On the other hand, model systems have been used for decades to develop therapies for a myraid of other conditions and disorders, and produced evidence-based treatments for not just autism but conditions from ADHD to schizophrenia. So why is there so much backlash about this line of research? The ASF podcast talks to Jill Silverman at UC Davis to get some perspective.

https://pubmed.ncbi.nlm.nih.gov/35285132

https://www.vox.com/future-perfect/377739/autism-research-mice-lab-models

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Animal models can explain heterogeneity

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Just like no two people are the same, no two strains of mice are the same. Using dozens of different strains of mice with and without a genetic mutation associated with autism called CHD8, researchers at University of Southern California showed great variability in the effect of this mutation on behaviors associated with neurodevelopmental disorders. This can reflect the great differences across people with autism and even people with a rare genetic syndrome associated with autism. It isn’t just one gene, it’s the other hundreds of genes that can contribute to susceptibility or resilience to different features of NDDs. One thing this study did not do was overlay environmental factors, which will also significantly influence the variability seen across the different background genetics in these mice.

https://pubmed.ncbi.nlm.nih.gov/36738737/

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Seizures and the after-effects depends on genetics

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In recognition of epilepsy awareness month, this week we are interviewing Jill Silverman and Nycole Copping from UC Davis who published a paper looking at the causes and consequences of seizures across 3 different strains of mice, which are identical all but their background genetics.  This is important because new animal models of autism are built upon these different background strains, but very little work has been done to really understand how these different tiny changes in genetic background influences response to an environmental factor.  In this study the environmental factor was a drug that produces seizures.  Two out of the three strains showed seizures and all three showed some behavioral after-effects of the seizure – inducing drug.  Therefore, differences in background genetics influenced the outcome of the mice, an effect that is rarely studied.  The authors point out what these behaviors are, what they mean, and why animal models are important for understanding ASD and seizures.

https://www.ncbi.nlm.nih.gov/pubmed/31698263

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Yeah, another study about autistic poop

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This week’s podcast includes a summary of the new study, this time in an animal model, looking at microbiome transplantation.  Because this was more of an experimental model, the researchers could be more rigorous in their design and look at things like behavior, brain activity, and specific biological pathways.  While a mouse does not have autism, transplantation of the autism microbiome resulted in autistic-like behaviors.   Second, a hopeful message of the value of participating in research on outcomes – those infants that were tracked prospectively showed improved outcomes later on, suggesting that all of the extra attention they get leads to a reduction in symptoms and an improvement in adaptive behavior.  Even if you do not have a family history of autism – participate in research.  It’s good for your child, and it’s good for other people’s children.

 

https://www.cell.com/cell/fulltext/S0092-8674(19)30502-1 

https://www.ncbi.nlm.nih.gov/pubmed/31032937