The structure of rat brain-derived neurotrophic factor (BDNF) gene is complex; four 5' exons are linked to separate promoters and one 3' exon is encoding the BDNF protein. To analyze the relative importance of the regulatory regions in vivo, we have generated transgenic mice with six different promoter constructs of the BDNF gene fused to the chloramphenicol acetyl transferase reporter gene. High level and neuronal expression of the reporter gene, that in many respects recapitulated BDNF gene expression, was achieved by using 9 kb of genomic sequences covering the promoter regions that lie adjacent to each other in the genome (promoters I and II and promoters III and IV, respectively) and by including sequences of BDNF intron-exon splice junctions and 3' untranslated region in the constructs. The genomic regions responsible for the in vivo upregulation of BDNF expression in the axotomized sciatic nerve and in the brain after kainic acid-induced seizures and KCl-induced spreading depression were mapped. These data show that regulation of the different aspects of BDNF expression is controlled by different regions in vivo, and they suggest that these promoter constructs may be useful for targeted expression of heterologous genes to specific regions of the central and peripheral nervous systems in an inducible manner.
Skip Nav Destination
Article navigation
1 January 1995
Article|
January 01 1995
Identification of brain-derived neurotrophic factor promoter regions mediating tissue-specific, axotomy-, and neuronal activity-induced expression in transgenic mice.
T Timmusk,
T Timmusk
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Search for other works by this author on:
U Lendahl,
U Lendahl
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Search for other works by this author on:
H Funakoshi,
H Funakoshi
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Search for other works by this author on:
E Arenas,
E Arenas
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Search for other works by this author on:
H Persson,
H Persson
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Search for other works by this author on:
M Metsis
M Metsis
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Search for other works by this author on:
T Timmusk
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
U Lendahl
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
H Funakoshi
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
E Arenas
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
H Persson
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
M Metsis
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1995) 128 (1): 185–199.
Citation
T Timmusk, U Lendahl, H Funakoshi, E Arenas, H Persson, M Metsis; Identification of brain-derived neurotrophic factor promoter regions mediating tissue-specific, axotomy-, and neuronal activity-induced expression in transgenic mice.. J Cell Biol 1 January 1995; 128 (1): 185–199. doi: https://doi.org/10.1083/jcb.128.1.185
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
Advertisement