By bringing back a gene that could be turned off that could be one of the causes of autism, the scientists saved the laboratory mice from a number of autistic symptoms.
As far as is known, autism has definite genetic roots, albeit as yet unclear. One of the main "suspects" is the Shank3 gene, which plays an important role in brain development and is defective in 1% of people with autism symptoms. The protein product of this gene in people without disturbances is found in the synapses, where it plays a structural role, ensuring the normal functioning of signaling molecules and proteins. It is logical to believe that the absence of the normal Shank3 gene or its decreased activity can serve as a neurological basis for the development of autism symptoms, including stereotyped behavior, difficulty in social interactions, and anxiety.
Indeed, a group of MIT professor Guoping Feng developed a special GM strain of laboratory mice with knockout of the Shank3 gene, whose representatives developed the corresponding autistic symptoms. Previously, scientists have already shown that in such mice, in some synapses (especially in the striatum) of the brain, a reduced number of dendritic spines - tubercles, which increase the efficiency of the contacts between neurons - are formed.
And recently, Guoping Feng and his team put new experiments on these mice. Scientists designed the Shank3 gene promoter so that they could turn it on at the right time. And when the mice reached adulthood and developed all the right symptoms, they did just that: they launched Shank3. As a result, some of the symptoms inherent in autism - stereotypical behavior and withdrawal from social interactions - really disappeared. At the cellular level, a return to the normal number of dendritic spines was observed in striatal synapses.
On the other hand, the result was not perfect. Anxiety and some violations of the coordination of movements still persisted. This led scientists to the idea that these manifestations may be associated with disturbances in the structure of synapses, which are already ripening and “fixed” by the adult state. To test this, the authors turned on the Shank3 gene in young (20-day-old) mice and eventually normalized the rest of the symptoms.
Now Guoping Feng and his colleagues have made every effort to find the optimal time for such an intervention, because in the future, when we learn to safely interfere with the working genome of a living organism, such an approach can give hope to many autists and their families. However, Shank3 is far from the only gene worth paying attention to, and scientists continue to struggle to reveal all the details of the development of these disorders.
Sergey Vasiliev