A Putative Genetic Disease Model of Schizophrenia

Schizophrenia is a complex neurodevelopmental disorder that affects approximately 1% of the population worldwide. Although research on schizophrenia is ongoing, little is still known about its origin. Schizophrenia is thought to result from a combination of genetic and environmental factors that ultimately lead to decreased brain volume and cortical thickness changes in energy metabolism or altered synaptic functioning. Several schizophrenia susceptibility genes have been discovered that encode proteins involved in synaptic plasticity, energy metabolism, transcription, apoptosis and neurogenesis. Stable Tubule Only Polypeptide (STOP) is a protein that has been shown to play a crucial role in neural development, normal synaptic functioning, and neurotransmission. In animals that lack STOP protein (STOP ko mice), profound abnormalities in synaptic transmission, metabolism and neural plasticity are found within the brain. In addition, these mice display several behavioral abnormalities, which have been correlated with deficits reported in human schizophrenic patients. Thus, the purpose of this research for the Brain Repair Centre was to compare total gene expression in the prefrontal cortex between STOP-knockout mice and their wild-type littermates. Since STOP ko mice provide a suitable model to investigate schizophrenia, it is of considerable interest to determine how a lack of this protein leads to abnormalities observed in these mice. A cDNA microarray was used for this investigation, which allows researchers to simultaneously assess changes in expression of over twenty-two thousand genes. The research revealed some novel insights into the alterations in signal transduction, energy metabolism, and synaptic plasticity that may contribute to schizophrenia neuropathology as well as validating the relevance of the STOP null mouse as an animal model for this psychotic disorder.

Faculty Supervisor:

Dr. George Robertson

Student:

Michael Thorne

Partner:

Brain Repair Centre

Discipline:

Pharmacy / Pharmacology

Sector:

Life sciences

University:

Dalhousie University