In certain instances, diseases manifest as complex physiological or behavioural phenotypes, which cannot be recapitulated in any in vitro model. An alternative strategy is to use xenograft systems in animal models where the endogenous organ has been genetically ablated (Kobayashi et al. 2010; Lee et al. 2014; Nagashima and Matsunari 2016). These may provide an opportunity to analyse such complex physiological and system-level phenotypes with human patient-derived cells, and potentially provide a source of such organs for transplantation in the future. Whilst such systems may be important for analysis of certain diseases, it is likely that most physiological defects result from inherent underlying molecular or cellular abnormalities. Therefore, cellular phenotypes such as gene expression changes or neuronal electrophysiology will not only help to ascertain the molecular mechanisms underlying complex disease phenotypes such as Alzheimer’s disease but also provide convenient measures for measuring the effects of genetic or pharmacological intervention.
