However, the applicability of results from these and other novel therapies to human disease is hampered by the relatively mild phenotype in both models, both of which have renal disease that is much less severe than the kidney-threatening disease seen in human SVV.
Interestingly, Li and co-workers reported a relatively mild phenotype in the human JAK2V617F-expressing model, which is consistent with many aspects of human ET, including a 5 10% rate of disease transformation to PV or myelofibrosis (Li et al., 2010).
These cycles of muscle degeneration/regeneration are suppressed by ~ age 3-4 months, but continues at low levels for the remainder of the mouse's lifetime [ 40], thereby producing the mild phenotype well-associated with the mdx model.
Currently the mdx mouse is the most widely used animal model of DMD, although its mild phenotype limits its suitability in clinical trials.
There are so many changes that are seen to a severe degree in definite AD and to a milder degree in normal ageing that this 'intermediate phenotype' model seems to make eminent sense.
One big limitation in the preclinical evaluation of the PTP modifiers is the fact that Col6a1−/− mice have such an extremely mild phenotype that they are probably best used as a model of mild BM (24).
Loss or depletion of VAPB activity in zebrafish, worms and mice induce a relatively mild phenotype possibly because of a functional redundancy between closely related VAP proteins in these models (Kabashi et al., 2013; Han et al., 2012).
Even though mdx mice show a mild phenotype and do not accurately reflect the severe nature of the human disease, they are considered a reasonable model.
Methylation studies confirmed X-inactivation was skewed moderately, but not completely, which is consistent with her mild phenotype.
A formal possibility for the mild phenotype could be partial hepatoblast-specific deletion of UPF2.
