  A variety of missense mutations and a stop mutation in the gene coding for
transmembrane protein 240 (TMEM240) have been reported to be the causative
mutations of spinocerebellar ataxia 21 (SCA21). We aimed to investigate the
expression of TMEM240 protein in mouse brain at the tissue, cellular, and
subcellular levels. Immunofluorescence labeling showed TMEM240 to be expressed
in various areas of the brain, with the highest levels in the hippocampus,
isocortex, and cerebellum. In the cerebellum, TMEM240 was detected in the deep
nuclei and the cerebellar cortex. The protein was expressed in all three layers
of the cortex and various cerebellar neurons. TMEM240 was localized to
climbing, mossy, and parallel fiber afferents projecting to Purkinje cells, as
shown by coimmunostaining with VGLUT1 and VGLUT2. Co-immunostaining with
synaptophysin, post-synaptic fractionation, and confirmatory electron
microscopy showed TMEM240 to be localized to the post-synaptic side of synapses
near the Purkinje-cell soma. Similar results were obtained in human cerebellar
sections. These data suggest that TMEM240 may be involved in the organization
of the cerebellar network, particularly in synaptic inputs converging on
Purkinje cells. This study is the first to describe TMEM240 expression in the
normal mouse brain.
