Use of the IMPC resource to inform psychiatric research

New publication by our partners at the German Mouse Clinic (Helmholtz Munich) and colleagues from INFRAFRONTIER and IMPC

Schizophrenia is a complex psychiatric disorder with genetic and phenotypic heterogeneity. Increasing information is available about rare and common disease risk variants, but there is still limited mechanistic insight. As a novel approach to this problem, this study leveraged the large-scale gene deletion mouse phenomic data provided by the International Mouse Phenotyping Consortium (IMPC), in conjunction with high-resolution brain region-specific gene expression data available from the Allen Brain Atlas and existing knowledge about human brain regions involved in Schizophrenia. Applying hierarchical clustering and weighted gene co-expression network analysis, we found a convergence of Schizophrenia risk and mouse prepulse inhibition genes based on telencephalic patterning. The associated neuronal genes were implicated in synaptic function and neurotransmission and overlapped with the greatest proportion of rare variants. Overall, this study provides a framework for utilising mouse preclinical genetics to explore both existing and novel human psychiatric disease candidate genes as druggable targets.

Original publication:
Garrett L, Trümbach D, Lee D et al. Co-expression of prepulse inhibition and schizophrenia genes in the mouse and human brain. Neuroscience Applied (2024). DOI: 10.1016/j.nsa.2024.104075