Spatial learning of mice lacking a neuron-specific epidermal growth factor family protein, NELL2.

NELL2 is a neuron-specific thrombospondin-1-like extracellular protein containing six epidermal growth factor-like domains. We previously disrupted the NELL2 gene in mice by gene targeting and showed that long-term potentiation is enhanced in vivo in the dentate gyrus of NELL2-deficient mice. To further elucidate the physiological roles of NELL2, we performed a behavioral characterization of NELL2(-/-) and their heterozygous control mice. NELL2-deficient mice exhibited learning impairment in the Morris water maze task. However, we observed no difference in passive avoidance learning between NELL2(-/-) and NELL2(+/-) mice. These observations suggest that NELL2 plays an important role in hippocampus-dependent spatial learning and that emotional learning does not depend critically on NELL2.