Model Organisms
Mouse model
As noted from the literature and available mouse models with loss of function or gain of function mutations in MEFV, mouse has been most commonly used as a model organism for MEFV mutations and inflammation. It is important to note that the protein homology shows that mice are missing the C terminal SPRY/B30.2 domain, which has been cited as a common location for missense mutations in disease [1]. However, mice appear to present with the same inflammatory response phenotype, with elevated interleukin-1beta levels, so the nonfunctional domain may not have an effect unless targeting an interactor of that domain, in which case a human copy of the gene could be "knocked in". Other Potential Model Organisms |
Figure 1. Human and Mouse pyrin comparison. Domain structures are labeled according to the key.
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In the literature, no other model organisms have yet been identified for studying the pyrin protein. Based on gene homology, there may be several candidates available that have not been utilized previously. Dogs have a shorter protein product (580aa), but retain all of the domains from primate species. Though less cost-effective than mice, this could be utilized as an option to study domain interactions outside of primates. Another candidate is the zebrafish; however the zebrafish homolog has not maintained the same function (erythropoeisis in fish) and has altered domains (RING domain instead of PYD) and therefore would make a poor model for studying MEFV. However, zebrafish could be used to study interactors with the B-box or SPRY domains, which were conserved in the bloodthirsty protein product.
References [1] Chae, Cho, Lee, Cheng, Liu, Feigenbaum, Katz and Kastner. 2011. Gain-of-Function Pyrin Mutations Induce NLRP3 Protein-Independent Interleukin-1b Activation and Severe Autoinflammation in Mice. Immunity 34: 755–768. |