Insight into HR-like PCD also comes from the characterization of mutants that exhibit accelerated cell death (acd) and defense activation in the absence of pathogen effectors.
A recent transcriptomic signature of Xpa -/- mouse dermal fibroblasts shows that suppression of ILS and activation of oxidative stress responses is also seen in DNA repair mutants that do not exhibit accelerated aging [ 47].
Our understanding of this process has significantly benefited from mutants that display either delayed or accelerated defense gene induction.
Accordingly, mouse mutants that are expected to display accelerated onset of liver fibrosis can be analysed after 2 weeks of continuous treatment.
We demonstrate that mutant huntingtin accelerates tumourigenesis in two mouse breast cancer models, increases epithelial mesenchymal transition (EMT) of cancer cells and favours lung metastasis in mice.
We show that mutant huntingtin accelerates tumourigenesis in two mouse breast cancer models, increases epithelial mesenchymal transition of cancer cells and thus favours lung metastasis in mice.
Similarly, it has been recently reported that Jag1 mutants reveal accelerated neurogenesis within its domains of expression, resulting in the overproduction of V1-derived interneurons [15].
In addition, it is worth noting that Sestrins are also expressed under normal unstressed conditions [ 1, 2, 4], and that dSesn knockout mutants show accelerated aging phenotypes even in the absence of any environmental stress [ 4].
We also show that the mutant significantly accelerates recovery kinetics from both open-inactivated and closed-inactivated states, findings that further suggest that recovery is coupled to deactivation [8] [10], [16], [23].
Because previous work done in our lab showed that mutants had an accelerated physical decline beginning around 40 days old, the increase in BDNF in acutely exercised mutants at 30 days of age may signify a critical time point when destabilizing neurologic changes begin to modify the mutant cerebellum.
