ACaenorhabditis elegansmodel to study dopamine transporter deficiency syndrome

• DOI: 10.1111/ejn.13366
• Publication Date: 2016-08-13T07:48:38Z
• Authors: Placido Illiano; Ambra Lanzo; Damiana Leo; Maria Paglione; Giuseppina Zampi; Raul R. Gainetdinov; Elia Di Schiavi
• Keywords: Loss function; Knockout mouse

Dopamine transporter deficiency syndrome (DTDS) is a novel autosomal recessive disorder caused by mutations in the dopamine (DAT), which leads to partial or total loss of function protein. DTDS pharmacoresistant and very little known about its neurobiology, part due lack relevant animal models. The objective this study was establish first model for with strong construct validity, using Caenorhabditis elegans, investigate vivo role played DTDS-related found human DAT (hDAT). We took advantage C. elegans knockout hDAT orthologue, cedat-1, obtain genetically humanized animals bearing hDAT, wild type two mutated forms (399delG 941C>T), null background. In transgenic expressing wild-type form, we observed rescue phenotype, as assessed well-established paradigms, be regulated endogenous uptake 6-hydroxydopamine (6-OHDA) DAT. less severe mutation (941C>T) able partially only one phenotypes, whereas 399delG impaired both phenotypic paradigms. Our findings demonstrate functional conservation between nematode validate previous vitro indications carriers mutations. Taken together, these observations fast inexpensive screening tests.