Cooperation in the cerebellum

By crossing knockout mice deficient for two cell adhesion molecules, Sakurai et al. have obtained the first genetic evidence for the molecules' functional overlap, and have explained why earlier tissue culture results were not replicated in single knockout mice (page 1259).

Sakurai and colleagues started by engineering mice deficient for NrCAM, which had only mild (∼11%) growth defects in two cerebellar lobes. When the authors crossed the NrCAM-deficient mice with existing mice that are deficient for the related cell adhesion molecule L1, the cerebellum of the double knockout was drastically reduced in size, and the mice were small and never survived later than eight days after birth. The mice probably die because their lack of coordination does not allow them to compete successfully for food.

The cerebellar defect may be largely a result of...