RediMODEL transgenics in C. elegans
HTR2A - serotonin receptor
- Function: HTR2A is a GPCR involved in synaptic neurotransmission response.
- Disease: Genetic defects in HTR2a have been found to be highly associated with Schizophrenia and bipolar disorder.
RediMODEL Kit - a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.
HTR2A RediMODEL KO: Generated in the C. elegans homolog ser-1 with a small deletion of coding sequence to create a knock-out (KO) strain. Loss of function from ser-1 deletion leads to hyperactivity and increased pharynx pumping rate. Major phenotype readout is the observation of pharyngeal pumping rate. An outcrossed version of the small deletion is currently available for preorder as gene knock-out.
HTRA2A RediMODEL KI: Generated in the C. elegans homolog ser-1 with human gene insertion to create a knock-in (KI) strain. Entire coding of ser-1 is replaced with wild-type HTR2A coding sequence. An HTR2A gene replacement is available for preorder as a humanized wt line.
HTR2A RediMODEL CV: Generated in the C. elegans homolog ser-1 with human gene insertion containing a clinical variant allele to create a clinical-variant (CV) strain. Entire coding of ser-1 is replaced with HTR2A coding sequence containing an amino-acid change polymorphism that has been observed in patient populations. Upon request, an HTR2A line with client-specific polymorphism is made as a clinical variant allele.
1. Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease, Maciel et al., Brain. 2015 Nov;138(Pt 11):3221-37. doi: 10.1093/brain/awv262. Epub 2015 Sep 15.
2. Behavioral adaptation in C. elegans produced by antipsychotic drugs requires serotonin and is associated with calcium signaling and calcineurin inhibition, Dwyer et al., Neurosci Res. 2009 Jul;64(3):280-9. doi: 10.1016/j.neures.2009.03.012. Epub 2009 Apr 5.
3. Three distinct amine receptors operating at different levels within the locomotory circuit are each essential for the serotonergic modulation of chemosensation in Caenorhabditis elegans, Harris GP1, Hapiak VM, Wragg RT, Miller SB, Hughes LJ, Hobson RJ, Steven R, Bamber B, Komuniecki et al., J Neurosci. 2009 Feb 4;29(5):1446-56. doi: 10.1523/JNEUROSCI.4585-08.2009.