Neurobehavioral changes in mice defective in semaphorin-triggered signalling

Abstract

Semaphorins and their receptors have diverse functions in axon guidance, organogenesis, angiogenesis, oncogenesis and immune regulation. Mutations in semaphorin genes are linked to several human neurological diseases, but their actual influence in the pathogenesis remains unclear. To get a clue to the crucial role of semaphorin-triggered signalling in brain homeostasis, we are currently examining the behavioral phenotypes of mice lacking semaphorins and their receptors. Sema4D/CD100 belongs to the class 4 semaphorins, which exhibit crucial roles in growth cone guidance of developing neurons. Our analyses disclosed accelerated motor behavior of Sema4D-deficient mice, suggesting the subtle alterations in the development of various central structures. We also present an aberrant behavioral phenotype of plexin-A1-deficient mice. The mutant mice showed impaired prepulse inhibition of acoustic startle, which is commonly observed in several neuropsychiatric diseases in humans including schizophrenia. Thus the study of the mutant mice may provide a molecular basis underlying the defects of schizophrenia and the related disorders. [J Physiol Sci. 2008;58 Suppl:S147]