Functional analysis of a minimal mouse serum amyloid A3 promoter in transgenic mice.
We report the generation of transgenic mice harboring the SAA3/LacZ transgene and analysis of its expression patterns in vivo following LPS-induced inflammation. Our results show that a 210-bp fragment of the mouse SAA3 promoter when placed in front of the LacZ gene was sufficient to confer basal and inflammation-induced reporter gene expression. Consistent with endogenous SAA3 expression, the basal level of LacZ expression was high in the lung and liver of newborn and 1-week-old transgenic mice. Its expression however decreased with increasing age and at 3-weeks ofage, LacZ expression was very low in the lung and was essentially undetectable in the liver. When SAA3/LacZ transgenic mice were injected with lipopolisaccharide to induce inflammation, beta-gal activities were increased approximately 6- and 16-fold in the lung and liver, respectively. Histological examination of lung and liver tissues stained with X-gal revealed that the LacZ transgene was expressed primarily in the macrophages. Thus, this minimal SAA3 promoter fragment contains the necessary regulatory sequences for its expression and cytokine responsiveness in macrophages albeit is insufficient to confer expression in hepatocytes.
Wang
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Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Liao
W S
WS
D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007763:Lac Operon; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D000685:Serum Amyloid A Protein / Q000235:genetics*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D008070:Lipopolysaccharides; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D001616:beta-Galactosidase