Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective.

摘要: Schizophrenia is a genetically complex disease considered to have neurodevelopmental pathogenesis and defined by broad spectrum of positive negative symptoms as well cognitive deficits. Recently, large genome-wide association studies identified common alleles slightly increasing the risk for schizophrenia. Among few schizophrenia-risk genes that been consistently replicated basic Helix-Loop-Helix (bHLH) transcription factor 4 (TCF4). Haploinsufficiency TCF4 (formatting follows IUPAC nomenclature: protein/protein function, Tcf4 rodent gene cDNA mRNA, human mRNA) causes Pitt-Hopkins syndrome-a characterized severe mental retardation. Accordingly, null-mutant mice display developmental brain defects. TCF4-associated are located in putative coding non-coding regions gene. Hence, subtle changes at level expression might be relevant etiopathology Behavioural phenotypes obtained with mouse model increased dosage electrophysiological investigations risk-allele carriers revealed an overlapping schizophrenia-relevant endophenotypes. Most prominently, early information processing higher functions appear associated genotypes. Moreover, recent study unravelled × environment interactions between smoking behaviour were specifically disrupted processing. Taken together, integrator ('hub') several bHLH networks controlling critical steps various developmental, and, possibly, plasticity-related transcriptional programs CNS also affect important Consequently, these findings support hypothesis schizophrenia provide basis identifying underlying molecular mechanisms.