Four-legged “Rain Man” provides new directions for autism research

By: /author/show/112 and Jigyasa Jyotika /The Daily Cardinal

UT-Southwestern scientists genetically engineer an antisocial, smart mouse

While searching for a mouse that exhibits the behaviors commonly seen in patients with autism, researchers at the University of Texas Southwestern Medical Center have stumbled upon a super smart yet socially awkward mouse similar to the loveable Raymond from the 1988 movie “Rain Man.”

Researchers hope the discovery of the “Rain Man” mouse will offer new insights into understanding autism, a disease that impacts more than 1.5 million people in the United States.

Autism is a complex brain disease caused during development and characterized by abnormalities in brain structure and function. According to Ellis Weismer, a UW-Madison professor of communicative disorders, autistic patients typically exhibit deficient communication, repetitive behavior and impaired social interactions.

Some scientists believe a patient’s genes may be partly to blame for autism. To better understand the genes implicated in autism, researchers study genetically engineered mice to express the common behaviors observed in patients with the disease.

Previous studies have led researchers to believe some cases of autism are linked to genetic mutations in neuroligins, molecules which adhere nerve cells together. Researchers at UT-Southwestern Medical Center administered a mutated human form of the neuroligin-3 molecule to mice and observed how the mice interacted socially with the normal mice in a cage.

While the average mouse spends time playfully wrestling and snuggling with other mice, the genetically engineered mice spent significantly less time socializing with other mice and more time with inanimate objects instead.

When it came to “mouse smarts,” the genetically engineered mice outdid their normal counterparts significantly in a “spatial ability” test. Although unproven in mice, spatial and mathematical abilities are linked significantly in humans, explained Thomas Südhof, a UT-Southwestern molecular genetics professor and senior author of the study.

“When you manipulate a brain, you usually don’t improve it,” Südhof said. “The fact that we get an improvement at all is very good. It shows we’re changing something specific.”

Researchers also examined how a mutated form of a brain molecule that helps bind nerve cells together affects brain signaling. In healthy brains, nerve cells work together to excite and inhibit brain signaling. An imbalance in signaling is thought to be involved in autism.

Nerve cells from the genetically engineered mice showed a significantly greater inhibitory action than their normal counterparts. This finding was a surprise, as previous studies have indicated that a loss of inhibitory action is possibly involved in autism.

“The results of the study are important because they show us how autistic symptoms are possibly generated by the developing brain and indicate that focusing on inhibitory action might be a way to treat autistic behaviors,” Südhof said.

While the UT findings offer new directions for autism research, Südhof cautioned that the “Rain Man” mouse offers only an approximation of a human condition.

“[Mouse models of autism are] an attempt to replicate, as best we can, a complicated disease that has, as a symptom, an inability to use language effectively,” Südhof said.