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Spectrum: Autism Research News

Cognition and behavior: Mutant mice show social deficits

by  /  28 September 2011
THIS ARTICLE IS MORE THAN FIVE YEARS OLD

This article is more than five years old. Autism research — and science in general — is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

Basic instinct: Mice lacking a signaling gene do not huddle over their pups or collect them when they are scattered around the cage.

Basic instinct: Mice lacking a signaling gene do not huddle over their pups or collect them when they are scattered around the cage.

Mice lacking a gene that regulates an important signaling pathway in the central nervous system have severe autism-like social deficits, including little interest in nurturing their offspring and problems with learning and memory, according to a study published 17 August in The Journal of Neuroscience1.

The results implicate the ERK2 gene, also called MAPK2, in autism. This gene is directly adjacent to the 22q11.2 chromosomal region, deletions of which have been linked to schizophrenia and autism. Mice that lack the gene in all tissues do not survive.

In the new study, researchers engineered mice lacking ERK2 only in cells of the central nervous system. These mice have little to no ERK2 in the cortex, hippocampus and cerebellum.

The mutant mice do not foster the offspring of control mice, and their own pups die after three days with no milk in their stomachs. The mutant pups do survive when raised by control mice, however. The mutant mothers also spend significantly less time huddling over their pups compared with controls and do not collect their pups when they are scattered around the cage.

The mice also show several other signs of social impairment, such as spending less time with novel mice than controls do, not recognizing sexual partners and being less likely than controls to build nests. They are also unusually aggressive: Reuniting mutant male siblings after two weeks apart leads to significantly more wounding compared with controls.

The study also found that the mutant mice roam around an open area and enter brightly lit spaces more often than controls do, suggesting that they are less anxious. They are also significantly less likely than controls to remember that a particular sound leads to a shock.

A 2010 study implicates the protein in fragile X syndrome, by showing that inhibiting the ERK1/2 proteins rescues elevated gene expression in the brains of fragile X mice.

References:

1: Satoh Y. et al. J. Neurosci. 31, 11953-11967 (2011) PubMed