Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome
Autor: | Stefano Espinoza, Damiana Leo, Loris Fichera, Raul R. Gainetdinov, Tatiana D. Sotnikova, Liudmila Mus, Evgeny A. Budygin, Caroline E. Bass, Placido Illiano |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Genetic enhancement Dopamine Population Genetic Vectors Gene Expression Biology medicine.disease_cause Article law.invention 03 medical and health sciences Mice 0302 clinical medicine law Transduction Genetic Gene Order medicine Animals Humans education Adeno-associated virus Gene Dopamine transporter Mice Knockout Neurons education.field_of_study Dopamine Plasma Membrane Transport Proteins Multidisciplinary Dopamine transporter deficiency syndrome Behavior Animal Gene Transfer Techniques Genetic Therapy Syndrome Dependovirus Phenotype Corpus Striatum 3. Good health Substantia Nigra Disease Models Animal 030104 developmental biology Treatment Outcome nervous system Recombinant DNA Cancer research biology.protein Female 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep46280 |
Popis: | Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this syndrome, displaying functional hyperdopaminergia and neurodegenerative phenotype leading to premature death in ~36% of the population. We used DAT-KO mouse as model for DTDS to explore the potential utility of a novel combinatorial adeno-associated viral (AAV) gene therapy by expressing DAT selectively in DA neurons and terminals, resulting in the rescue of aberrant striatal DA dynamics, reversal of characteristic phenotypic and behavioral abnormalities, and prevention of premature death. These data indicate the efficacy of a new combinatorial gene therapy aimed at rescuing DA function and related phenotype in a mouse model that best approximates DAT deficiency found in DTDS. |
Databáze: | OpenAIRE |
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