This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Knockouts and Knockdowns
No NOD2 associated RNAi were identified by databases probing. This is understandable given that the only non-mammal homolog found was Zebrafish nod2. Zebrafish morpholino knockdowns and several mouse knock outs of NOD2 homologs were identified. Mouse knockouts were obtained from the Mouse Genome Informatics website and zebrafish knockdowns were obtained from Oehlers et al. [1]. The following table lists the effects of each of these knockouts/knockdowns.
Mouse KnockoutsZebrafish knockdown |
System(s) affected
immune, skeleton, mortality, hematopoietic, homeostasis, immune
immune, digestive, hematopoietic, homeostasis, cellular immune, mortality, digestive, growth, hematopoietic, homeostasis immune immune immune decreased resistance to salmonella infection, decreased expression of dual oxidaze in larva |
Analysis
All knockouts and knockdowns are implicated in altered immune function. This agrees well with our understanding of NOD2's role in Crohn's Disease. Particularily, Nod2tm1Daph mimics mutation SNP13, one of the most common Crohn's Disease associated variants in humans. Such a knockout mouse would provide a good model in which to study new treatments for Crohn's Disease. Morpholino knockdown in zebrafish also provides a good model. The use of zebrafish provides the added benefit of transparent larvae, making evaluation of disease state much simpler, though the percent homology is much less than that of the mouse model.
References
[1] Oehlers SH, Flores MV, Hall CJ, Swift S, Crosier KE, Crosier PS. The inflammatory bowel disease (IBD) susceptibility genes NOD1 and NOD2 have conserved anti-bacterial roles in zebrafish. Dis Model Mech. 2011;4(6):832-41.
[2] Mouse Genome Informatics
[2] Mouse Genome Informatics