As predicted by the caretaker model, mutants deficient in Sae2 or the related nuclease Mre11 also gave lower expansion rates, and double mutant analysis supported a pathway involving both Rpd3 and Mre11 (Fig. 2B).
However, there was no formation of stress granules, as measured by ICC, and PABP remained diffuse throughout the cytoplasm, indicating that in this cellular model mutant FUS in the cytoplasm does not directly induce, or become recruited to, stress granules.
In the model, mutants are generated during cell division.
In the B. tribocorum rat infection model, deletion mutants in virB4 and virD4 failed to get bacteraemic, thus demonstrating an essential role for the VirB/VirD4 system in establishing intraerythrocytic infection (Schulein and Dehio, 2002).
In the second model, mutant huntingtin was expressed in the photoreceptors.
Analysis of the corresponding linker mutants provided results comparable to EspP, with transport inactive Pet mutants T573, A576 and F589 located within Domain 2 of our Pet model, and active mutants in the flanking β-helical core region (Fig. 4B).
Our response: To compare this we needed models of appropriate mutants, in complexed and uncomplexed states.
Earlier modeling of these mutants in yeast (Fontanesi et al., 2004) also concluded that they impair translocase activity and lead to a defect in oxidative phosphorylation (OXPHOS).
As many current anthelmintics, including PZQ, are agonists, it would be worthwhile developing systems for gain-of-function mutants in model organisms (for example using targeted overexpression banks).
