Taking a bird's eye view on a mouse model review:a comparison of findings from mouse models targeting DISC1 or D/SC7-interacting proteins

摘要

DISCI has garnered much interest from researchers trying to understand the neurobiology of psychiatric disease. DISCI appears to function as a structural protein hub for a number of molecules, many of which are considered disease-relevant targets in their own right. Thus, in this article, we compare behavioral, anatomical and biochemical findings in genetic mouse models of DISCI and D/SC7-interacting proteins to better understand how dysfunction of DISCI and/or its interactors could contribute to psychiatric pathophysiology through convergent effects on distinct cells, circuits and behaviors. Consistencies in phenotypes across mouse models suggest that DISCI and its binding partners are particularly critical for working memory performance, proper neuronal migration and cortical volume, normal spine density, an intact monoaminergic system, proper levels of parvalbumin and normal cytokine/stress signaling in the rodent. If these DISCI functions translate to humans, it would explain how alterations in DISCI or DISCI interactors could contribute to psychiatric pathophysiology. Identification of such a biological convergence will hopefully improve the development of novel therapeutics for patients by focusing efforts on specific domains that are affected by D/SC7-related genetic risk architecture.