2 min readStudy Makes Progress Toward Mouse Model of Human Autism
San Francisco, CA – Researchers from UC San Francisco have reportrd linking autism in a mouse model of the disease with abnormalities in specific regions of the animals’ chromosomes.
The regions contain genes associated with aberrant brain development and activity.
“These discoveries in mice may eventually pave the way towards understanding autism in human patients and devising new treatments,” said co-senior author, Dr. Elliott H. Sherr, a paediatric neurologist at UCSF Benioff Children’s Hospital and professor of neurology at UC San Francisco (UCSF).
The findings are reported in a study published on April 15 in PLOS One.
The scientists bred a group of normal mice with a line of genetically modified mice that exhibit behaviours which are the mouse equivalent of autism. The 400 descendants of that crossbreeding, explained Sherr, “had a random assortment of genetics – some normal and healthy, some aberrant.”
The scientists exhaustively observed and recorded the behaviour of each descendant mouse. Since each animal’s genetic makeup was already known, the researchers were able to pinpoint associations between specific autistic behaviours and specific chromosomal regions.
“This allowed us to say which regions we think contain the genes that contribute to which behaviour,” said Sherr.
Sherr noted that those regions “contain genes that are already known to cause autism in humans, or are involved in brain development in such a way that makes it likely that they can cause autism.”
To test for autistic behaviour, the mice were put in the middle chamber of an enclosure with three chambers. In the chamber on one side was another mouse; in the other, an inanimate object. “Mice are social animals, so a normal mouse would spend much more time in the chamber with the other mouse,” said Sherr. “An autistic mouse would spend more time with the object, or equal time with the object and the other mouse, because it didn’t care.”
The researchers also observed what the mice did when they were in a chamber together. “A healthy mouse will spend a lot of time sniffing or interacting with the other mouse, while an autistic mouse will roam around the chamber ignoring the other mouse as if it was inanimate,” said Sherr.
The research will have a number of potential benefits, he said, particularly once researchers pinpoint the exact locations of the genes on the chromosomes. “Having the genes means that you can begin to pick apart the connection between the genes and the actual behaviour, and look at how the mutation on a gene might result in aberrant behaviour. Having an animal model means that you can look at the anatomy in a more careful way, study the cells in a tissue culture dish and manipulate them in other ways.”
Scientists will also be able to test the effects of exposure to toxins and other substances on the development of autism, he said.
Eventually, said Sherr, “Having an animal model will let us test potential drugs to treat autism.”
Publication: Dorothy M. Jones-Davis equal contributor, Mu Yang equal contributor, Eric Rider, Nathan C. Osbun, Gilberto J. da Gente, Jiang Li, Michael D. Weber, Saunak Sen, Jacqueline Crawley, Elliott H. Sherr. Quantitative Trait Loci for Interhemispheric Commissure Development and Social Behaviors in the BTBR T+ tf/J Mouse Model of Autism. PLOS One (2013). http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0061829