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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
1996-1-30
pubmed:abstractText
To study the molecular basis of tissue-specific and hormonally regulated expression of the fatty acid synthase (FAS) gene in vivo, we generated lines of transgenic mice carrying 2.1 kilobases of the 5'-flanking region (-2100 to +67) of the rat FAS gene fused to a chloramphenicol acetyltransferase (CAT) reporter gene. This reporter gene construct was strongly expressed in tissues that normally express high levels of FAS mRNA, which include liver and white adipose tissues. In contrast, CAT reporter activity was not detected in appreciable levels in lung, heart, kidney, and muscle tissues, which do not normally show significant levels of FAS activity. The relative levels of the CAT mRNA driven by the rat FAS promoter in various tissues of the transgenic animals approximated those of the endogenous mouse FAS mRNA. We also examined the hormonal and nutritional regulation of the FAS(2.1)-CAT reporter gene in transgenic mice. CAT activity was increased in both liver and white adipose tissue when fasted animals were refed a high carbohydrate, fat-free diet. These changes in CAT activity and CAT mRNA levels occurred in parallel to the changes in endogenous mouse FAS mRNA levels. On the other hand, fasting/refeeding did not change CAT activity appreciably in other tissues, such as muscle and brown adipose tissue. Administration of dibutyryl cAMP at the start of refeeding prevented an increase in CAT activity in liver. However, the cAMP effect was tissue-specific as cAMP treatment did not bring about change in CAT activity in adipose tissue. Next, to examine the effect of insulin, we made the transgenic mice insulin-deficient by streptozotocin treatment. Insulin treatment of the streptozotocin-diabetic mice increased both the CAT activity and CAT mRNA levels driven by the rat FAS promoter in liver and white adipose tissue. These changes in CAT expression by insulin paralleled those in endogenous FAS mRNA levels. Administration of glucocorticoids increased CAT activity in all tissues examined: liver, white and brown adipose tissues, lung, heart, and spleen. Overall, the first 2.1 kilobases of the 5'-flanking region of the rat FAS gene appear to contain sequence elements necessary to confer tissue-specific and hormonally regulated expression characteristic of the endogenous FAS gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30339-43
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:8530458-Adipose Tissue, pubmed-meshheading:8530458-Adipose Tissue, Brown, pubmed-meshheading:8530458-Animal Nutritional Physiological Phenomena, pubmed-meshheading:8530458-Animals, pubmed-meshheading:8530458-Base Sequence, pubmed-meshheading:8530458-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:8530458-DNA Primers, pubmed-meshheading:8530458-Diabetes Mellitus, Experimental, pubmed-meshheading:8530458-Diet, pubmed-meshheading:8530458-Diet, Fat-Restricted, pubmed-meshheading:8530458-Dietary Carbohydrates, pubmed-meshheading:8530458-Fasting, pubmed-meshheading:8530458-Fatty Acid Synthetase Complex, pubmed-meshheading:8530458-Gene Expression, pubmed-meshheading:8530458-Gene Expression Regulation, Enzymologic, pubmed-meshheading:8530458-Glucocorticoids, pubmed-meshheading:8530458-Insulin, pubmed-meshheading:8530458-Liver, pubmed-meshheading:8530458-Mice, pubmed-meshheading:8530458-Mice, Transgenic, pubmed-meshheading:8530458-Molecular Sequence Data, pubmed-meshheading:8530458-Muscle, Skeletal, pubmed-meshheading:8530458-Organ Specificity, pubmed-meshheading:8530458-Polymerase Chain Reaction, pubmed-meshheading:8530458-Promoter Regions, Genetic, pubmed-meshheading:8530458-RNA, Messenger, pubmed-meshheading:8530458-Rats, pubmed-meshheading:8530458-Recombinant Fusion Proteins
pubmed:year
1995
pubmed:articleTitle
Hormonal and nutritional control of the fatty acid synthase promoter in transgenic mice.
pubmed:affiliation
Department of Nutritional Sciences, University of California, Berkeley 94720, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.