The lacZ gene under the control of the 7 kb of human dystrophin muscle specific promoter is expressed in cardiac muscle but not in adult skeletal muscle in transgenic mice.
In previous transgenic studies, we reported a 0.9 kb fragment from a mouse dystrophin muscle promoter that contains the regulatory elements required for expression of dystrophin only in the right heart. In this study, to further characterize the regulation of muscle type of promoter, we analyzed promoter activity and tissue specificity using a total 14 kb fragment around the human dystrophin muscular-specific exon 1 in vitro and in vivo. In vitro analysis showed that the lacZ construct of the 7 kb promoter and 7 kb intron 1 was expressed 2.5 times as strong as the lacZ construct of only the 7 kb promoter in C2/4 myotubes. In vivo analysis revealed expression of both constructs in the whole heart, skeletal muscle and vascular smooth muscle in embryos. However, in adults, the expression in skeletal muscle disappeared. We conclude that the 7 kb upstream region and the 7 kb intronic region included responsible elements for the expression in the heart, but not in skeletal muscle in vivo. It is possible that a strong enhancer element for skeletal muscle exists in some other region.
Ogawa
M
M
Department of Child Development, Kumamoto University School of Medicine, 1-1-1 Honjou, Kumamoto, Japan.
Kaname
T
T
Kimura
S
S
Kawasaki
I
I
Nomura
K
K
Suzuki
M
M
Miike
T
T
Yamamura
K
K
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D015152:Blotting, Northern; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D016189:Dystrophin / Q000235:genetics*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005697:Galactosides / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017930:Genes, Reporter / Q000235:genetics; D007211:Indoles; D007763:Lac Operon / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*
D016189:Dystrophin; D005697:Galactosides; D007211:Indoles; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside