Scientists from Italy and Russia have developed a model for studying the rare but very serious neural system disease Dopamine Transporter Deficiency Syndrome, (DTDS).
Dopamine is a one of main neurotransmitters in the brain. Dopamine neurons release it during their excitation. Dopamine transporter is a specific protein responsible for pumping dopamine back into the neuron following its release. Dopamine transporter is a target for psychostimulants such as cocaine and amphetamines. DTDS – is the new genetic disorder first described in 2011. It is caused by a mutation in the gene encoding the dopamine transporter. Children with this syndrome show evident neurological symptoms and are not able to learn, to walk or talk.
Raul Gainetdinov, Skoltech professor and Director of the Institute of Translational Biomedicine SPbU: “Dopamine transporter – is a main subject of my lab work. Several years ago, we have developed mice with a mutation in the dopamine transporter and found that 30-40% mice die during lifetime showing special neurological disorders. Just recently, several children with severe loss-of-function mutations in the dopamine transporter gene and similar neurological manifestations have been identified. In this investigation, we attempted to recreate the same human mutations in round worms (Caenorhabditis elegans, C. elegans). It turned out that С. elegans is a very good model for studying DTDS causing mutations“.
In this work Raul Gainetdinov and his collaborators (Placido Illiano, Elia Di Schiavi and others) showed that classical biology model object – C. elegans is well suited for DTDS studies. Researchers deleted it’s own dopamine transporter and inserted human mutant protein. Two different models were developed with two different mutations: with more and less severe disease forms. Scientists compared mutated worms behavior and dopamine transporter functioning by using a specific toxin. This toxin kills dopamine neurons selectively, getting into the cell through the dopamine transporter. It helped to estimate the deficiency of dopamine transporter function. If the transporter completely ineffective, the dopamine cells survive because the toxin can not penetrate into the cell.
13 mutations leading to DTDC are already found and most likely several more will be found soon. Using the method proposed it is possible to investigate functional consequences of such mutations quite fast. Such experiments in worms take just a few weeks.
Raul Gainetdinov’s lab is focused on the development of new approaches for studying and curing brain diseases. The main targets are schizophrenia, Parkinson’s disease, attention deficit hyperactivity disorder (ADHD) and others. Significant attention is paid for new research models development.
Results of this study were published in European Journal of Neuroscience.
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The Skolkovo Institute of Science and Technology (Skoltech) is a private graduate research university in Skolkovo, Russia, a suburb of Moscow. Established in 2011 in collaboration with MIT, Skoltech educates global leaders in innovation, advances scientific knowledge, and fosters new technologies to address critical issues facing Russia and the world. Applying international research and educational models, the university integrates the best Russian scientific traditions with twenty-first century entrepreneurship and innovation.: https://www.skoltech.ru/
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