RediMODEL transgenics in C. elegans
LRRK2 - leucine-rich repeat kinase
- Function: LRRK2 is a leucine-rich repeat kinase necessary for stability of dopaminergic neurons.
- Disease: Genetic defects in LRRK2 have been found to be highly associated with Parkinson's Disease.
RediMODEL Kits - a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.
LRRK2 RediMODEL KO: Generated in the C. elegans homolog lrk-1 is an early gene deletion as a 3-frame STOP allele which leads to loss of gene expression. The resulting lrk-1 deletion knock-out (KO) results in decreased neuronal activity near the pharynx. Major phenotype readout for KO line is an observation of reduced pharynx pumping with exposure to oxidative stress. An 3-frame STOP mutant is currently available for preorder as gene knock-out.
LRRK2 RediMODEL KI: Generated in the C. elegans homolog lrk-1 with human gene insertion to create a knock-in (KI) strain. Entire coding of lrk-1 is replaced with wild-type LRRK2 coding sequence. An LRRK2 gene replacement is currently available for preorder as a humanized wt line.
LRRK2 RediMODEL CV: Generated in the C. elegans homolog lrk-1 with human gene insertion containing a clinical variant allele to create a clinical variant (CV) strain. Entire coding of lrk-1 is replaced with LRRK2 coding sequence containing amino-acid change polymorphism that has been observed in patient populations. Upon request, an LRRK2 line with client-specific polymorphism is made as a clinical variant allele.
1. Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans, Feng et al., PLoS One. 2011;6(8):e22354. doi: 10.1371/journal.pone.0022354. Epub 2011 Aug 3.
2. The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research, Cookson et al., Biochem J. 2016 Feb 1;473(3):221-32. doi: 10.1042/BJ20150985.
3. Chaperone complex BAG2-HSC70 regulates localization of Caenorhabditis elegans leucine-rich repeat kinase LRK-1 to the Golgi, Hisamoto et al., Genes Cells. 2016 Apr;21(4):311-24. doi: 10.1111/gtc.12338. Epub 2016 Feb 8.