Six of the rats each lack one autism candidate gene — FMR1, NLGN3, MeCP2, NRXN1, CACNA1C and PTEN — and a seventh lacks mGluR5, which encodes a neuronal signaling receptor that is important in fragile X syndrome.
The impetus for making the rat models is to make autism research more attractive to the pharmaceutical industry. The standard approach in the industry is to test dosage and toxicology in rats, not in mice.
“Unless there’s investment, it doesn’t matter how many great ideas — which tend to be risky — you generate, they will not proceed forward,” says Robert Ring, vice president of translational research at the advocacy organization Autism Speaks. The idea is not to replace mice, Ring adds, but “to begin creating complementary animal models that help facilitate translational research.”
Over the past few months, Richard Paylor at Baylor College of Medicine in Houston, Texas, has done behavioral testing on young rats missing FMR1 — mutations in which lead to fragile X syndrome — and NLGN3, one of the first genes implicated in non-syndromic autism.
Unexpectedly, some of the rat behaviors are the opposite of what’s seen in their mouse counterparts: The FMR1-deficient rats engage in social play less than controls do, for example, whereas some strains of mice lacking FMR1 have more social interactions than controls.
Rats missing either FMR1 or NLGN3 also show some unexpected new characteristics, such as severe female aggression and compulsive chewing on water bottles.
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