What happened when the environment met DISC1? Showing the interactive effects of poly I:C and DISC1 on mouse phenotypes related to mood disorders.

摘要

The understanding of the function of disrupted in schizophrenia 1 (DISCI) has continued relentlessly since it was cloned in 2000 (1). Discovered at the breakpoint of a balanced translo-cation t(1 ;11), which segregates with major mental illness in a large Scottish family, it is now known to play a role in many fundamental neuronal processes including synaptic plasticity and neurogenesis, which all have plausible roles in disease etiology (2). The strength of the association to disease in the original pedigree and the compelling tone of the since emergent biology has insured that it has remained center-stage in the midst of the redefinement of the genetic architecture of mental illness through the results from genome-wide association studies and copy number variation identification. One of the vital areas that has propelled this field is the generation and characterization of a number of DISC1 mouse models. These models come in many different flavors already, from the naturally occurring 25 base-pair deletion found in the 129 mouse strain (and likely other strains as well) to the two /V-ethyl-/V-nitro-sourea-generated point mutant mice, which both have single amino acid changes (Q31L and LI OOP) and have been deemed to have "depressive" and "schizophrenic" phenotypes, respectively (3,4). Because each mouse model has been characterized in different laboratories across the globe, it is too difficult to make robust comparisons across models. But within models it is clear that each has a phenotype, be it behavioral or anatomical, that can be linked to what we think we know about mental disease when modeled in mice (5).