Mouse models also fail to reflect the long periods of time often required for disease evolution in humans, particularly for the neurodegenerative disorders. For example, Huntington’s disease takes many years to evolve in humans, and to accelerate the process in mice, transgenics have been constructed that express much longer polyglutamine expansions than those appearing in nature. Perhaps as a result, none of the many types of nominally Huntington disease mice thus far developed faithfully replicate both the typical disease course and neuropathology of the disease in humans (Brooks and Dunnett, 2015; Howland and Munoz-Sanjuan, 2014; Menalled and Brunner, 2014). As such, whether cell therapeutic strategies modeled in these mice will prove as efficacious in HD patients remains an uncomfortable unknown.
