Schizophrenia Daily News Blog

Progress Toward Better Animal Models of Psychiatric Disorders

A recent news story in Nature magazine delves into the biological aspects of schizophrenia. It discusses how animals, specifically mice, are being used to "model" different diseases so that we can more clearly understand them in humans. In the past decade biologists have developed ways to genetically modify mice to make them develop specific disorders and diseases. This allows scientists to more easily identify the function of specific genes involved with genetically influenced disorders, and then find out what treatments work best against these disorders. Genetically modified mice with modified or non-mice genes are called transgenic mice.

The story discusses new research specifically aimed at improving animal models of human psychiatric disorders. The goal of this research is to aid our understanding of psychiatric disorders and treatments. Laurence Tecott, a research psychiatrist at the University of California, San Francisco states that "...the reason we have not seen a genuinely new class of drug in psychiatry for 50 years...is largely because animal models are woefully inadequate representations of human-specific disorders." According to the story, many scientists support Tecott's position, however Eric Nestler, a neuroscientist at the University of Texas Southwestern Medical Center points out, "...sensible (animal) models of important aspects of the neurobiology underpinning psychiatric disorders are just around the corner."

Here are a few recent research advances the story discusses:

The discovery of "...a strong candidate gene has been identified — that encoding the protein DISC-1...Psychiatrist Akira Sawa, from the Johns Hopkins University...has created transgenic mice with a disrupted Disc-1 gene and used brain scanning to show that such mice have enlarged brain ventricles (cavities in the brain) — especially on the left side..." This seems to be a promising model since the same areas are enlarged in the brains of humans suffering from schizophrenia.

Another research psychiatrist, Alcino Silva, at the University of California, Los Angeles, "has gone a step further. His team has created a transgenic mouse in which the Disc-1 gene can be switched on or off at will. He found that activation of the gene on just one specific day — the seventh after birth — was sufficient to cause a range of symptoms analogous to those seen in schizophrenia later in life."

Yet another researcher, neurobiologist Guoping Feng, at Duke University Medical Center discovered a biomarker, or "neural circuit...relevant to disease...identified in people using techniques such as functional magnetic resonance imaging (fMRI), which measures changes in oxygenation of blood flowing through the brain." Feng knocked out a gene (which means he removed a gene that is usually naturally present in mice). The gene he knocked out called a Sapap3 is responsible for encoding "a key protein involved in regulating receptors for the neurotransmitter glutamate. He noticed that the genetically altered mice groomed themselves until they bled" and thus he created an animal model for obsessive-compulsive disorder.

Animal models enable us to understand mental illness, and as a result, possibly improve our methods for testing medications that treat symptoms of these illnesses.

For more information see: Dr. Philip Seeman's interview regarding animal models and antipsychotic medications.

Full Nature Magazine Story: Model behavior

A good resource on knock out genes: Howard Hughes Medical Institute, Knocking Out Genes to Mimic or Cure Disease