Researchers Engineer Genetically Altered Mice to Study 'Autistic' Social Deficits

Mice genetically engineered to display social interaction deficits are apt models for studying some autism spectrum disorders in people, according to researchers from the Howard Hughes Medical Institute and the University of Texas Southwestern Medical Center.

"The scientists said the mice they developed may represent an important advance in modeling autism spectrum disorders in mice, offering researchers a new tool for understanding how specific defects in neural development may lead to autism," the Medical Institute noted in a statement issued September 6. You can view the full statement here.

The reason this is an advance, according to lead investigator Thomas C. Südhof, is that researchers were able to isolate the social problems in their laboratory subjects. "What sets this mouse model apart is that the mouse shows highly selective social deficits and memory enhancement, but as far as we can tell, no other pathologies. This makes it a potentially useful model for a subset of people with ASDs with just such characteristics," Südhof said. Other experiments using mice to simulate autistic symptoms don't demonstrate this kind of finely-tuned subject, he said.

The researchers published a study in the online publication Science Express, which posted a free brief abstract here. More information about the biochemistry and neuroscience in the research comes from the press release:

The researchers engineered mice that have a single mutation in the gene for a protein called neuroligin-3. This protein functions as a cell adhesion molecule in synapses, the junctions that connect neurons in the brain and allow them to communicate with each other. Synapses are essential to all brain activities, such as perception, behavior, memory, and thinking. Südhof said that the neuroligin-3 mutation that his team recapitulated in the mice has been identified in some people with ASDs. Mutations in proteins that interact with neuroligin-3 have also been detected in some people with ASDs.

Proper function of the brain depends on a delicate balance between excitatory and inhibitory electrophysiological signaling among neurons. Südhof and his colleagues found that this balance was disrupted in the mutant mice, which showed an increase in the signaling of inhibitory neurotransmitters. In contrast, they found that knocking out the neurologin-3 gene entirely produced no such imbalance.

The most striking behavioral abnormality they observed in the mutant mice was an impaired ability to interact socially with other mice. However, the animals showed enhanced spatial learning and memory. They were more able than normal mice to learn and to remember the location of a platform submerged in murky water.

The online publication MedPage Today picked up on this research to explain the information above, while also giving guidance to its audience of doctors about what to tell patients. It gives two pieces of advice:

Explain to patients who ask that the research described here was conducted only in mice, and that it is not known whether the same findings apply to people.

Explain that the genetic mutation the authors described is seen in only a small percentage of people with autism spectrum disorders.

This is good context for laypeople, too, of course. One can imagine, with all the media coverage of healthcare and medical research studies that doctors get bombarded with questions about stories they hear or read in the news—including questions about autism, with the rising caseload and broadening awareness we're experiencing.

This particular study is the second research effort to focus on genetically engineering mice. Also see:

* Scientists Report Reversing Symptoms of Autism in Mice