RediMODEL transgenics in C. elegans
SLC6A3 - dopamine transporter
- Function: SLC6a3 is an integral membrane protein responsible for transporting the dopamine neurotransmitter from synaptic space back into presynaptic neurons.
- Disease: Genetic defects in SLC6A3 have been found to be highly associated with Infantile Parkinsonism-Dystonia.
RediMODEL Kits - a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.
SLC6A3 RediMODEL KO: Generated in the C. elegans homolog dat-1 with deletion of coding sequence to create a knock-out (KO) strain. Loss of function from dat-1 deletion leads to build up of dopamine neurotransmitter at the synapse. Major phenotype readout is the observation of paralysis upon exposure to liquid with the Swimming Worm Induced Paralysis (SWIP) assay. An all-coding deletion mutant is currently available for preorder as gene knock-out.
SLC6A3 RediMODEL KI: Generated in the C. elegans homolog dat-1 with human gene insertion to create a knock-in (KI) strain. Entire coding of dat-1 is replaced with wild-type SLC6A3 coding sequence. A SLC6A3 gene replacement is available for preorder as a humanized wt line.
SLC6A3 RediMODEL CV: Generated in the C. elegans homolog dat-1 with human gene insertion containing a clinical variant allele to create a clinical-variant (CV) strain. Entire coding of dat-1 is replaced with SLC6A3 coding sequence containing an amino-acid change polymorphism that has been observed in patient populations. Upon request, a SLC6A3 line with client-specific polymorphism is made as a clinical variant allele.
1. Sequence determinants of the Caenhorhabditis elegans dopamine transporter dictating in vivo axonal export and synaptic localization, Blakely et al., Mol Cell Neurosci. 2017 Jan;78:41-51. doi: 10.1016/j.mcn.2016.11.011. Epub 2016 Nov 30.
2. An Open-Source Analytical Platform for Analysis of C. elegans Swimming Induced Paralysis, Blakely et al., J Neurosci Methods. 2014 Jul 30; 232: 58–62. Published online 2014 May 2. doi: 10.1016/j.jneumeth.2014.04.024.
3. Vigorous motor activity in Caenorhabditis elegans requires efficient clearance of dopamine mediated by synaptic localization of the dopamine transporter DAT-1, Blakely et al., J Neurosci. 2007 Dec 19;27(51):14216-27.