The proximal region of the MBP gene promoter is sufficient to induce oligodendroglial-specific expression in transgenic mice.
To characterize regulatory DNA sequences involved in oligodendroglial expression of myelin basic protein (MBP), transgenic mice carrying a 256 bp fragment of the mouse MBP promoter fused to an Escherichia coli lacZ gene were generated. Of four transgenic families, two (lines 2 and 4) expressed beta-galactosidase activity in the nervous system but not in most other tissues. Histochemical and immunohistochemical analysis of adult brain from these two lines showed oligodendroglial-specific expression of the transgene. In line 2, only a small proportion of oligodendrocytes expressed the transgene, and in labelled cells the product of the enzymatic reaction with beta-galactosidase was confined to a small round vesicle in the vicinity of the nucleus. In contrast, in tissue sections from line 4 adult brain and spinal cord beta-galactosidase activity was much more intense and at least 80-90% of oligodendrocytes expressed the transgene. Detection of the MBP-lacZ transcript by in situ hybridization showed that the transgene mRNA was confined to the oligodendrocyte cell body. These results suggest that cis-acting regulatory elements, specifying oligodendrocytes identity, are located within 256 bp upstream from the MBP gene.
Goujet-Zalc
C
C
Laboratoire de Neurobiologie Cellulaire, Moléculaire et Clinique, INSERM U-134, Hôpital de la Salpêtrière, Université Pierre et Marie Curie, Paris, France.
Babinet
C
C
Monge
M
M
Timsit
S
S
Cabon
F
F
Gansmüller
A
A
Miura
M
M
Sanchez
M
M
Pournin
S
S
Mikoshiba
K
K
Zalc
B
B
D000375:Aging / Q000502:physiology; D000818:Animals; D005260:Female; D015870:Gene Expression; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics*; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
D004676:Myelin Basic Protein; D012333:RNA, Messenger