RediMODEL transgenics in C. elegans
HTT - huntingtin
- Function: HTT is thought to contribute to normal development.
- Disease: Genetic defects causing disease are primarily gain of function mutations from poly-nucleotide expansions coding for long stretches of poly-glutamine (poly-Q).
RediMODEL Kits - a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.
HTT RediMODEL KO: Generated in the C. elegans homolog F21G4.6 as a large deletion allele leading to over 100% deletion in the coding sequence. The F21G4.6 deletion knock-out (KO) results in loss of expression of in F21G4.6. A major phenotype readout for KO line has yet to be observed. The all-coding deletion mutant is currently available as gene knock-out.
HTT RediMODEL KI: Generated in the C. elegans homolog F21G4.6 with human gene insertion to create a knock-in (KI) strain. Entire coding of F21G4.6 is replaced with wild-type HTT coding sequence. An HTT gene replacement is currently available for preorder as a humanized wt line.
HTT RediMODEL CV: Generated in the C. elegans homolog F21G4.6 with human gene insertion containing a clinical variant allele to create a clincal variant (CV) strain. Entire coding of F21G4.6 is replaced with HTT coding sequence containing amino-acid change polymorphism that has been observed in patient populations. Upon request, a HTT line with client-specific polymorphism is made as a clinical variant allele.
1. AMPK activation protects from neuronal dysfunction and vulnerability across nematode, cellular and mouse models of Huntington's disease, Neri et al., Hum Mol Genet. 2016 Mar 15;25(6):1043-58. doi: 10.1093/hmg/ddv513. Epub 2015 Dec 17.
2. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington's disease, Pei et al., Drug Des Devel Ther. 2016 Apr 13;10:1443-51. doi: 10.2147/DDDT.S94666. eCollection 2016.
3. A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles, Kikis et al., PLoS One. 2017 Mar 10;12(3):e0173644. doi: 10.1371/journal.pone.0173644. eCollection 2017.