Different regulatory sequences are required for parvalbumin gene expression in skeletal muscles and neuronal cells of transgenic mice

Abstract

Parvalbumin (PV) is expressed in fast-twitch fibers in skeletal muscles and a subpopulation of inhibitory neurons in the CNS. We generated transgenic mice that expressed the human interleukin-2 receptor α-subunit–green fluorescent fusion protein (hIL-2R–GFP) using two types of PV transgene. One contained the hIL-2R–GFP gene downstream of a 16.5-kb 5′-upstream PV genomic sequence (PV line). The other comprised the hIL-2R–GFP gene in bacterial artificial chromosome (BAC) with either a 180-kb (PA line) or 155-kb (PB line) insert encompassing the PV gene. Independent lines of all transgenic mice showed a faithful hIL-2R–GFP expression in fast-twitch muscle fibers. However, appreciable hIL-2R–GFP expression in the CNS occurred only in the PA transgenic lines. In one line of PA transgenic mice, hIL-2R–GFP was properly expressed in PV-containing neurons in the cerebellum, thalamic reticular nucleus, globus pallidus and cerebral cortex, though ectopic expression was observed in a particular subset of cerebellar astrocytes. Another line of PA transgenic mice showed a selective and mosaic expression of hIL-2R–GFP in PV-containing Purkinje, basket and stellate cells in the cerebellum. These results indicate that the 16.5-kb PV genomic sequence is sufficient for fiber-type-selective transcription but additional regulatory sequences comprised in BAC DNA are required for proper expression in PV-containing neurons.