Abstract
Sez12 is a seizure-related gene, which exhibits a down-regulated expression in mouse brain after a pentylenetetrazol-induced seizure. The Sez12 protein is a transmembrane protein encoding the C-type lectin domain in its extracellular region, which is probably involved in cell-cell interaction. Sequence analysis of the Sez12 provided a mouse homologue of the human DGCR2/IDD gene lying within the DiGeorge syndrome critical region, whose hemizygous deletion causes a developmental disorder, termed Velocardiofacial/DiGeorge syndrome (VCFS/DGS). VCFS/DGS patients display malformations in multiple systems, as well as an increased frequency of neuropsychiatric defects including schizophrenia. To examine the physiological and pathological involvement of the Sez12, we generate mice with a deletion in the Sez12 gene. Several Sez12 knockout mice displayed long-lasting seizure-like activity, and abnormal gait and rotarod performance. Histological analysis of these Sez12 knockout mice showed vacuolated perikarya in the Purkinje cell layer, where the expression of the knock-in gene encoding the green fluorescence protein was prominent. However, there was no pathological change in the skeletal muscle involved in some behavioral abnormalities. These findings suggest that the behavioral phenotypes of Sez12 knockout mice are caused by a deficiency of the cell-cell interaction through the Purkinje cells. [J Physiol Sci. 2008;58 Suppl:S148]
