One-gene change makes mice neurotic.

Forget the rhymes threatening their tails with a carving knife. These mice are so timid that they panic at a butter knife and possibly at butter.

Researchers at the Salk Institute and the Scripps Research Institute in La Jolla, Calif., have engineered mice that are hypersensitive to stress and display a mousy version of anxiety. The project suggests new targets for antidepressants and antianxiety drugs, says senior researcher Kuo-Fen Lee of Salk.

The worrywart mice, for example, show peak levels of the stress hormone ACTH after only 2 minutes of being held in restraints. Regular mice take five times that long to get so stressed.

Tracy L. Bale and her colleagues created the neurotic mice by knocking out the Crhr2 gene, which encodes receptors for CRH, and UCN, which are substances that have been linked to stress. They describe the work in the April NATURE GENETICS, which includes two other teams' papers on the Crhr2 gene.