Developmental expression of rat torsinA transcript and protein

A GAG deletion in the gene (TOR1A) for torsinA is associated with childhood-onset generalized dystonia (DYT1). Environmental factors may contribute to development of the phenotype since mutations in TOR1A are clinically penetrant in less than 40% of cases. Median age of onset is 10 and appearance of dystonia after 28 is rare. As a step towards understanding the temporal window of DYT1 disease penetrance, we have examined torsinA transcript and protein expression in rats from the embryonic period through adulthood. With relative quantitative multiplex real-time RT-PCR, we detected torsinA transcript in both neural (cerebellar cortex, striatum, cerebral cortex, thalamus and hippocampus) and non-neural (liver, kidney and heart) tissues at each developmental time point tested (embryonic day 20 [E20], postnatal day 1 [P1], P7, P14, P36, 6 months, 1.5 years). Levels of torsinA transcript were highest at E20 or P1 in all tissues examined except for the cerebellum where transcript levels peaked at P14. Early postnatal levels of torsinA transcript were over three times higher than those seen in adult rats. With quantitative radioactive in situ hybridization, torsinA transcript was widely distributed in brain at all ages with levels peaking at P14 in both cerebellum and striatum. TorsinA-immunoreactivity (IR) was present in neurons throughout the brain. TorsinA-IR was detected in perikarya, dendrites and axons but not nuclei. At P14, prominent expression of torsinA was noted in both striatal cholinergic interneurons and cerebellar Purkinje cells. Our results suggest that torsinA may contribute to postnatal maturational events in the brain such as dendritic arborization and synaptogenesis. Furthermore, the time course of torsinA expression in discrete components of motor networks is compatible with the temporal window of clinical penetrance in DYT1 mutation carriers.