The POSITION is for study of astrocyte-specific transcription, with application of findings to production of transgenic mice to investigate CNS development/function and for gene therapy. The gene being analyzed is that encoding glial fibrillary acidic protein (GFAP), the major component of astrocyte intermediate filaments. This gene is of interest because of its repertoire of regulatory responses: its expression is almost exclusively limited to astrocytes, is developmentally regulated, and is responsive to injury. Projects underway are described under Research Program. One particularly well-suited for a graduate student thesis involves brain-region specificity of GFAP expression. We have observed that a GFAP promoter consisting of about 2 kb of 5’-flanking DNA drives expression of transgenes throughout the brain, but that a promoter consisting of two subsegments of this fragment is active only in the cortex, hippocampus and caudal vermis of the cerebellum, but not in other brain regions. This result reveals an unexpected and sharply defined regional heterogeneity among astrocytes. Progressive replacement of the missing GFAP 5’-flanking DNA should reveal novel transcriptional controls responsible for the region-specific expression. This information should provide insight into the functional consequences of astrocyte heterogeneity, and permit construction of transgene expression cassettes that target specific brain regions.