With the number of genetic risk factors linked to schizophrenia at over a hundred and counting, finding the right ones to follow is the field's next big challenge. A team at Duke University has simplified the problem by focusing on a molecular pathway containing risk mutations, and, by manipulating a downstream effector, has created a mouse model that unites three phenotypes of the disease previously thought to be unrelated.
The model could serve as a tool for exploring the biology of schizophrenia, and contribute to preclinical screening of new therapies.
On the whole, there is a growing movement away from creating models in mice that purportedly mimic the disease because of the complexity of assigning human behavioral phenotypes to animals. "You cannot make a schizophrenic mouse. You can only model certain aspects of the disease," said Guoping Feng, a professor of neuroscience at Massachusetts Institute of Technology (MIT).
On the other hand, he added, "Genetic mouse models that alter cellular and molecular pathways will help us understand how those pathways are involved in schizophrenia. From a cellular and molecular point of view, this will be a very good model for studying the disease."
Many of the risk factors in schizophrenia cluster in pathways that influence synaptic function, which has led researchers to increasingly view the disease as one of synaptic connectivity. One hypothesis is that effects of synaptic disturbances propagate through circuits of interconnected neurons.
The team, led by Scott