Rapid activation of astrocyte-specific expression of GFAP-lacZ transgene by focal injury.
Astrocytes form a key cellular component of the central nervous system. They respond vigorously to diverse neurologic insults by undergoing hypertrophy and increasing expression of the glial fibrillary acidic protein (GFAP) gene, but their functions are largely unknown. To analyze astrocytes in vivo we constructed a transgenic vector from GFAP gene sequences and monitored its efficiency by fusing it to lacZ. Injection of the GFAP-lacZ hybrid gene into the germline of mice yielded six different lines of transgenic mice. In all lines the expression of lacZ was astrocyte-specific. In unmanipulated transgenic animals beta-galactosidase activity was much more prominent in astrocytes of the hippocampal formation, selected white matter tracts, and glial limitans than in astrocytes of other areas. This pattern of expression illustrates the physiologic heterogeneity of astrocytes and probably reflects differences in functional demands placed on these cells in different brain regions. Upmodulation of transgene expression was used to determine the time frame within which astroglial activation and increased GFAP gene expression occur following a neurologic insult. Induction of GFAP-lacZ expression was detectable within 1 hour after focal mechanical trauma. This demonstrates that the response of astrocytes to neurologic injury is very rapid and implies that these cells could fulfill important early functions in wound healing within the central nervous system.
Mucke
L
L
Department of Neuropharmacology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Oldstone
M B
MB
Morris
J C
JC
Nerenberg
M I
MI
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005798:Genes, Bacterial; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D011993:Recombinant Fusion Proteins