Mice Expressing Human Genes Bred To Help Unravel Mental Disorders
New mouse strains engineered to express human genes related to mental disorders are being developed under a recently-launched grant program from NIMH’s Division of Neuroscience and Basic Behavioral Science. The new models are designed to help scientists understand the molecular workings of variations in genes that may predispose for – or even help protect against – illnesses like depression, bipolar disorder and schizophrenia. They will also explore how duplications or the differences in the amount of genetic material affect brain function, and how genes influence response to treatments.
The new studies follow a spate of recent discoveries using such mouse models to replicate features of mental and developmental disorders. So far, eight new grants have been awarded in response to an NIMH program announcement issued last year.
“Knock-In” to Model Bipolar Features
In one of the newly launched studies, Elizabeth Simpson, Ph.D., of the University of British Columbia, is following-up her recent discovery* of eight variants of a suspect gene in people with bipolar disorder, schizophrenia and aggressive disorders that were not found in healthy controls. Conserved through evolution, this gene is important for brain development and birth of new neurons in both the mouse and human forebrain. Simpson initiated her search for variants in humans after finding that mice lacking the gene are hyperactive, aggressive and otherwise behaviorally impaired.
Instead of such a “knock-out,” her new study will “knock-in” combinations of the suspect human gene variants in an effort to create mouse strains that mimic features of the mental illnesses, particularly bipolar disorder. The researchers will generate five different mouse strains and test them for differences in brain systems, behavior, and any effects of the gene variants on response to lithium, the medication commonly used to prevent episodes of mania and depression. They hope their findings will ultimately contribute to better diagnosis and treatment of the disorder.
Depression Gene Riddle Examined in Mouse Embryonic Stem Cells
In another of the newly-funded studies, Beverly Koller, Ph.D., of the University of North Carolina, will genetically engineer mice to express human gene variants at the center of a controversy in psychiatric genetics.