Cognition and behavior: Rett syndrome mice are social

Mice with a mutation in the Rett syndrome gene are more social than controls, according to a study published 11 September in Behavioral Genetics. The results, based on detailed observation of social behavior, support previous studies showing that Rett syndrome mouse models do not have severe social deficits.

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: Glass houses: A see-through cage that mimics a wild burrow allows researchers to see how mice spend their time in natural situations.

Mice with a mutation in the Rett syndrome gene are more social than controls, according to a study published 11 September in Behavioral Genetics¹. The results, based on detailed observation of social behavior, support previous studies showing that Rett syndrome mouse models do not have severe social deficits.

In humans, deletion of the MeCP2 gene, which is located on the X chromosome, is usually fatal in boys. In girls, it leads to Rett syndrome, an autism-related disorder.

Researchers often study male mice with mutations in MeCP2 because they have severe symptoms earlier in life than females do. These studies have found conflicting results on the mutations’ effect on social behavior, however: Some studies have suggested that Rett syndrome mice are less social than controls², but others have reported the opposite³.

Studies have also shown that mice with a MeCP2 mutation have deficits in learning and memory and display repetitive behaviors.

In the new study, researchers observed the social behavior of male mice with a mutation that truncates the MeCP2 protein. Rather than just noting whether the mice approach others, as most studies do, the researchers manually recorded subtle distinctions in the interactions.

For example, in one assay, researchers put the mice into large see-through cages that mimic burrows in the wild. As the mice interact, the researchers note details such as whether they touch one another’s nose, rear or the sides of their face and whether they try avoid the other mouse or just ignore it.

In these burrows, MeCP2 mutant mice are more likely than controls to interact with other mice by touching their noses and to huddle together in the dark, the study found. This is consistent with previous studies showing that a mutation in MeCP2 boosts sociability in mice.

The researchers also placed pairs of mice into small cages that force them to interact. Under these conditions, the MeCP2 mutant mice are again more likely than controls to touch noses. They also crawl over and under each other more often than controls do, the new study found.

BTBR mice, an inbred strain of mice that mimic many of the social deficits in autism, show this same crawling behavior, which researchers have been able to rescue with anti-anxiety drugs. Crawling under another mouse as if it were an object might be a way to avoid social contact in a tight space, the researchers say.

The MeCP2 mice are no more likely than controls to play with toys in a repetitive manner, suggesting that they do not have restricted interests. They also show only subtle differences in grooming, licking their tails and paws only a little more often than controls do.

The results suggest that MeCP2 mutant mice are social, but that they could have subtle social anxiety as seen in the crawling behavior. Based on their observations, mice lacking the Rett syndrome gene might not be a good model for autism-like social deficits, the researchers say.