Antisense and differentiation.
The use of antisense technology in animals has great potential for studying individual genes and for generating animal models of human disorders. Further control can be obtained by the use of inducible promoters to regulate the expression of antisense constructs, so that the timing and degree of antisense inhibition can be manipulated. In addition, tissue-specific promoters and enhancers provide the potential for targeting antisense inhibition to specific organs. Transgene expression in mice directed by the Cyp1a-1 promoter and enhancer elements can be increased in the liver up to 10,000-fold by administration to the animals of the inducer, 3-methylcholanthrene. Transfected antisense constructs containing splice site regions of the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene can reduce HPRT activity to less than 1% of levels in parental NIH-3T3, COS, or HeLa cells. Antisense constructs including splice site regions and driven by the inducible Cyp1a-1 promoter should prove to be powerful tools in generating mouse models of human disorders.
Caskey
C T
CT
Institute for Molecular Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
D000199:Actins / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002645:Chickens; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis
D000199:Actins; D016372:RNA, Antisense; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D015500:Chloramphenicol O-Acetyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase