Many of the original reports of social deficits in mice have not held up when tested by independent labs — including Silverman’s — or in different strains of mice. Inconsistent findings have plagued studies not just of SHANK3 mice, but also those with mutations in the risk genes CHD8, NLGN3, NLGN4 and CNTNAP2, among others. That has left many scientists wondering whether mice can ever recapitulate something as complex and human as autism.
“I think that defining an autism mouse is folly,” says Valerie Bolivar, director of the Mouse Behavioral Phenotype Analysis Core at the Wadsworth Center in Albany, New York. “To get all those things in a nice, neat package with a bow — we’re just not going to get that.”
A more productive approach may be to focus only on behaviors that are reproducible in mice, such as quantitative measures of how the animals learn. If researchers do want to get at social deficits, they may need to go back to basics and methodically catalog mouse behavior.