Molecular approaches for studying astrocytes

Abstract

In the year 2007, literally hundreds of research papers were published that utilize molecular approaches to study the role of astrocytes in neurophysiology and neurological disorders. This is striking given that the molecular tools for selectively perturbing gene expression in astrocytes were developed just over a decade ago. Two investigators stand out as pioneers in this area, Drs. Michael Brenner and Albee Messing. While at National Institutes of Health, Mike Brenner carried out studies mapping the transcriptional regulatory elements of the promoter for glial fibrillary acidic protein (GFAP) (Masood et al., 1993), an intermediate filament protein expressed exclusively by mature astrocytes in the CNS. This information was absolutely essential in order to develop a regulatory unit (promoter) small enough to be handled by the molecular techniques available in the early 1990s and yet sufficient to target expression constructs to astrocytes in vivo and in vitro. In 1994, Mike Brenner together with Albee Messing and colleagues published a paper demonstrating that a 2.2-kb fragment of the 5'-flanking sequence of the human GFAP (hGFAP) promoter was sufficient to direct transgene expression in the majority of astrocytes in vitro and in vivo without significant expression in other cell types in brain (Brenner et al., 1994). Thanks to the generosity of Mike Brenner, the 2.2-kb fragment of the human GFAP promoter has been provided to hundreds of investigators throughout the world without restrictions or required collaborations. Further, the collaborative effort of Mike Brenner and Albee Messing has provided a series of important insights into the role of astrocytes in brain, culminating most recently in their discovery that the aberrant expression of GFAP is involved in Alexander'fs disease (Messing and Brenner, 2003). Those of us working in this area owe these investigators a debt of gratitude for the development and dissemination of reagents important in the molecular analysis of astrocytes.