Differences in the activation of the GFAP gene promoter by prion and viral infections.
The expression of glial fibrillary acidic protein (GFAP), a component of astroglial intermediate filaments, is regulated under developmental and pathological conditions. After surgical injury or viral infections, an increase in this protein reflects reactive gliosis in the brain. We analyzed the activation of the GFAP gene in transgenic mice using a prion and two different viruses (rabies and Theiler viruses). Inoculation of the transgenic mice with the C506M3 mouse prion strain resulted in activation of the GFAP-lacZ transgene. Expression of the GFAP transgene increased concomitantly with the expression of GFAP in astrocytes from the infected mice. In contrast, infection with rabies or Theiler's virus had no effect on the expression of the GFAP transgene, showing that the glial reactions to these infectious agents involved different mechanisms. These findings indicate that the activation of the endogenous GFAP gene as a consequence of viral infection could involve different regulatory pathways than activation as a result of prion infection. The first 2 kb upstream from the start codon of the GFAP gene seems to provide enough activation domains to produce efficient activation of the reporter gene in prion-infected mice.
Titeux
Matthias
M
Biologie Moléculaire de la Différenciation, Université Paris-7, Case Postale 7136, 2 Place Jussieu, 75005 Paris, France.
Galou
Maria
M
Gomes
Flávia Carvalho Alcantara
FC
Dormont
Dominique
D
Neto
Vivaldo Moura
VM
Paulin
Denise
D
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D020805:Central Nervous System Viral Diseases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics* / Q000378:metabolism; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017945:Theilovirus / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
D005904:Glial Fibrillary Acidic Protein