RediMODEL transgenics in C. elegans
UNC13A - synaptic vesicle release regulator
- Function: UNC13A is needed for coordinated neurotransmitter release at synapses.
- Disease: Genetic defects in UNC13A have been found to be highly associated with Amyotrophic Lateral Sclerosis (ALS).
RediMODEL Kits - a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.
UNC13A RediMODEL KO: Generated in the C. elegans homolog unc-13 with framshifting microdeleltion (s69) creates a knock-out (KO) strain by eliminating coding for a significant portion of the last half of the gene. Loss of function from unc-13 frameshift mutation leads to uncoordinated movement. Major phenotype readout is the observation of deviation in pharyngeal pumping. An outcrossed version of (s69) frameshifting SNP is currently available for preorder as gene knock-out.
UNC13A RediMODEL KI: Generated in the C. elegans homolog unc-13 with human gene insertion to create a knock-in (KI) strain. Entire conserved coding of unc-13 is replaced with wild-type UNC13A coding sequence. A UNC13A gene replacement is available for preorder as a humanized wt line.
UNC13A RediMODEL CV: Generated in the C. elegans homolog unc-13 with human gene insertion containing a clinical variant allele to create a clinical-variant (CV) strain. Entire coding of unc-13 is replaced with UNC13A coding sequence containing an amino-acid change polymorphism that has been observed in patient populations. Upon request, a UNC13A point-mutant line with a client-specific polymorphism is made as a clinical variant allele.
2. C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: a genome-wide meta-analysis, Veldink et al., Ann Neurol. 2014 Jul;76(1):120-33. doi: 10.1002/ana.24198. Epub 2014 Jun 27.