Seaver Autism Center researchers at Icahn School of Medicine at Mount Sinai have published a study in Disease Models and Mechanisms demonstrating that the range of mouse phenotypes caused by a Shank3 gene mutation does not depend on varied genetic backgrounds. This finding indicates the high level of transferability of research findings in mouse models to those in rat models.
Phelan-McDermid Syndrome (PMS) is a rare genetic syndrome in which one copy of the q13 portion of chromosome 22 is missing or mutated leading to global developmental delay, delayed or absent speech, and autistic behaviors. There is overwhelming evidence available indicating that SHANK3, a gene coding for a protein essential to neuronal communication, causes the neurological and behavioral aspects of the syndrome. In addition, the Shank3 mutation can lead to a range of phenotypes.
When a range of phenotypes is present, it can mean that a combination of genes impact the phenotype. It is this varied genetic background which is present in people affected by Fragile X syndrome, for example. In this study, researchers tested whether the range of phenotypes caused by Shank3 mutations is caused by varied genetic backgrounds.
The researchers, led by Dr. Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center at Mount Sinai, tested three different strains of mice, each with a different genetic background. The goal of this was to discern whether the genetic background is responsible for the varied phenotypes caused by Shank3 mutations. After an extensive battery of tests designed to assess the main features of PMS, the researchers found that there were very modest differences in the phenotypes between the three strains of mice.
This finding indicates that varied genetic backgrounds are not the cause of the spectrum of phenotypes found in people with PMS. Rather, it suggests that there are other modifiers at work to cause the spectrum of phenotypes seen in people with PMS, and further tests are required in order to identify these modifiers. This lack of causation by varied genetic backgrounds is significant because it demonstrates that findings made in mouse models are very likely transferable to rat models, and rat models are a promising new direction for model systems in autism.
Other researchers involved in the study include Drs. Elodie Drapeau, Nate P. Dorr, and Gregory A. Elder.
For more information and to read the paper, click here.
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