RediMODEL transgenics in C. elegans
STXBP1 - syntaxin binding protein
- Function: STXBP1 is a regulator of synaptic vesicle release allowing coordinated release of neurotransmitters into the synapse.
- Disease: Genetic defects in STXBP1 have been found to be highly associated with infantile epileptic encephalopathy.
RediMODEL Kits - a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.
STXBP1 RediMODEL KO: Generated in the C. elegans homolog unc-18 is a precision deletion allele which leads to the removal of the entire coding sequence. The unc-18 deletion knock-out (KO) results in loss of function in coordinated vesicle release. Major phenotype readout for KO line is the observation of severly uncoordinated (paralyzed) animal. The all-coding deletion mutant is currently available as gene knock-out.
STXBP1 RediMODEL KI: Generated in the C. elegans homolog unc-18 with human gene insertion to create a knock-in (KI) strain. Entire coding of unc-18 is replaced with wild-type STXBP1 coding sequence. An STXBP1 gene replacement is currently available for preorder as a humanized wt line.
STXBP1 RediMODEL CV: Generated in the C. elegans homolog unc-18 with human gene insertion containing a clinical variant allele to create a clincal variant (CV) strain. Entire coding of unc-18 is replaced with STXBP1 coding sequence containing amino-acid change polymorphism that has been observed in patient populations. Upon request, an STXBP1 line with client-specific polymorphism is made as a clinical variant allele.
1. Structure-function study of mammalian Munc18-1 and C. elegans UNC-18 implicates domain 3b in the regulation of exocytosis, Barclay et al, PLoS One. 2011 Mar 21;6(3):e17999. doi: 10.1371/journal.pone.001799.
2. Rab-3 and unc-18 interactions in alcohol sensitivity are distinct from synaptic transmission, Barclay et al., PLoS One. 2013 Nov 14;8(11):e81117. doi: 10.1371/journal.pone.0081117. eCollection 2013.
3. Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression, Poduri et al., Ann Neurol. 2017 Mar;81(3):419-429. doi: 10.1002/ana.24883. Epub 2017 Feb 14.