RediMODEL transgenics in C. elegans
SLC6A4 - serotonin transporter
- Function: SLC6A4 is an integral membrane protein responsible for transporting the serotonin neurotransmitter from synaptic space back into presynaptic neurons.
- Disease: Genetic defects in SLC6A4 have been found to be highly associated with Depressive Disorder.
RediMODEL Kits - a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.
SLC6A4 RediMODEL KO: Generated in the C. elegans homolog mod-5 with deletion of coding sequence to create a knock-out (KO) strain. Loss of function from mod-5 deletion leads to increased neurotransmission due to serotonin build up at the synapse. Major phenotype readout is the observation of a 5-fold increase in serotonin dependent pumping of pharynx muscle. An all-coding deletion mutant is currently available as gene knock-out.
SLC6A4 RediMODEL KI: Generated in the C. elegans homolog mod-5 with human gene insertion to create a knock-in (KI) strain. Entire coding of mod-5 is replaced with wild-type SLC6A4 coding sequence. A SLC6A4 gene replacement is currently available as a humanized wt line.
SLC6A4 RediMODEL CV: Generated in the C. elegans homolog mod-5 with human gene insertion containing a clinical variant allele to create a clinical-variant (CV) strain. Entire coding of mod-5 is replaced with SLC6A4 coding sequence containing an amino-acid change polymorphism that has been observed in patient populations. Upon request, a SLC6A4 line with client-specific polymorphism is made as a clinical variant allele.
1. Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans, Sze et al., J Neurosci. 2011 Jun 15;31(24):8948-57. doi: 10.1523/JNEUROSCI.1692-11.2011.
3. Mutations in the Caenorhabditis elegans serotonin reuptake transporter MOD-5 reveal serotonin-dependent and -independent activities of fluoxetine, Horvitz et al., J Neurosci. 2001 Aug 15;21(16):5871-84..