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Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice
Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration. Chimeric genes were constructed containing 152...
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Published in: | The Journal of biological chemistry 1990-08, Vol.265 (22), p.13344-13350 |
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creator | ADRIAN, G. S BOWMAN, B. H FUNMEI YANG HERBERT, D. C WEAKER, F. J ADRIAN, E. K ROBINSON, L. K WALTER, C. A EDDY, C. A RIEHL, R PAUERSTEIN, C. J |
description | Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human
TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration.
Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding
region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes
containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing
TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher
than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels
are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration
in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload.
Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human
TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the
molecular basis of transferrin regulation throughout mammalian development into the aging process. |
doi_str_mv | 10.1016/S0021-9258(19)38304-8 |
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TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration.
Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding
region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes
containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing
TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher
than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels
are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration
in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload.
Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human
TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the
molecular basis of transferrin regulation throughout mammalian development into the aging process.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(19)38304-8</identifier><identifier>PMID: 2376597</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>Animals ; Base Sequence ; Biological and medical sciences ; Chimera ; Chloramphenicol O-Acetyltransferase - genetics ; Chloramphenicol O-Acetyltransferase - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression - drug effects ; genes ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Plasmids ; promoters ; RNA, Messenger - genetics ; RNA, Messenger - isolation & purification ; Transcription, Genetic ; Transferrin - biosynthesis ; Transferrin - genetics</subject><ispartof>The Journal of biological chemistry, 1990-08, Vol.265 (22), p.13344-13350</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-5ea9d5b7d12595152d0b2d0745048eff6647561b4fe0d8c8dad35ae5e5bb1fe03</citedby><cites>FETCH-LOGICAL-c441t-5ea9d5b7d12595152d0b2d0745048eff6647561b4fe0d8c8dad35ae5e5bb1fe03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19548724$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2376597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ADRIAN, G. S</creatorcontrib><creatorcontrib>BOWMAN, B. H</creatorcontrib><creatorcontrib>FUNMEI YANG</creatorcontrib><creatorcontrib>HERBERT, D. C</creatorcontrib><creatorcontrib>WEAKER, F. J</creatorcontrib><creatorcontrib>ADRIAN, E. K</creatorcontrib><creatorcontrib>ROBINSON, L. K</creatorcontrib><creatorcontrib>WALTER, C. A</creatorcontrib><creatorcontrib>EDDY, C. A</creatorcontrib><creatorcontrib>RIEHL, R</creatorcontrib><creatorcontrib>PAUERSTEIN, C. J</creatorcontrib><title>Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human
TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration.
Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding
region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes
containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing
TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher
than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels
are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration
in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload.
Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human
TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the
molecular basis of transferrin regulation throughout mammalian development into the aging process.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Chimera</subject><subject>Chloramphenicol O-Acetyltransferase - genetics</subject><subject>Chloramphenicol O-Acetyltransferase - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>genes</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Plasmids</subject><subject>promoters</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - isolation & purification</subject><subject>Transcription, Genetic</subject><subject>Transferrin - biosynthesis</subject><subject>Transferrin - genetics</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><recordid>eNpFkF9rFTEQxYMo9Vr9CIV9UNGHrZkks5s8Sqm2UPChKr6FbDLbG9k_1-Qu1m_f3N6lBkImZ86cgR9jZ8DPgUPz6ZZzAbURqD-A-Si15KrWz9gGuJa1RPj1nG2eLC_Zq5x_83KUgRN2ImTboGk37OfVMrqp2ic35Z5SitN5dXm_S5RznKfKTaGKqRTjHJbB7Q_a3Fd-G0dK0Vd3NFGu4hpQfkUbo6fX7EXvhkxv1veU_fhy-f3iqr759vX64vNN7ZWCfY3kTMCuDSDQIKAIvCu3VciVpr5vGtViA53qiQftdXBBoiMk7Doomjxl74-5uzT_WSjv7Rizp2FwE81LtoCtwVaqYsSj0ac550S93aU4uvTPArcHnvaRpz3AsmDsI0-ry9zZumDpRgpPUyvA0n-39l32bugLBh_z_3CDSrfisP_t0beNd9u_MZHt4uy3NFrRoBXCgpRKyQf8F4o9</recordid><startdate>19900805</startdate><enddate>19900805</enddate><creator>ADRIAN, G. S</creator><creator>BOWMAN, B. H</creator><creator>FUNMEI YANG</creator><creator>HERBERT, D. C</creator><creator>WEAKER, F. J</creator><creator>ADRIAN, E. K</creator><creator>ROBINSON, L. K</creator><creator>WALTER, C. A</creator><creator>EDDY, C. A</creator><creator>RIEHL, R</creator><creator>PAUERSTEIN, C. J</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T3</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19900805</creationdate><title>Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice</title><author>ADRIAN, G. S ; BOWMAN, B. H ; FUNMEI YANG ; HERBERT, D. C ; WEAKER, F. J ; ADRIAN, E. K ; ROBINSON, L. K ; WALTER, C. A ; EDDY, C. A ; RIEHL, R ; PAUERSTEIN, C. 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Psychology</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>genes</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>Plasmids</topic><topic>promoters</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - isolation & purification</topic><topic>Transcription, Genetic</topic><topic>Transferrin - biosynthesis</topic><topic>Transferrin - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ADRIAN, G. S</creatorcontrib><creatorcontrib>BOWMAN, B. H</creatorcontrib><creatorcontrib>FUNMEI YANG</creatorcontrib><creatorcontrib>HERBERT, D. C</creatorcontrib><creatorcontrib>WEAKER, F. J</creatorcontrib><creatorcontrib>ADRIAN, E. K</creatorcontrib><creatorcontrib>ROBINSON, L. K</creatorcontrib><creatorcontrib>WALTER, C. A</creatorcontrib><creatorcontrib>EDDY, C. A</creatorcontrib><creatorcontrib>RIEHL, R</creatorcontrib><creatorcontrib>PAUERSTEIN, C. J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Human Genome Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ADRIAN, G. S</au><au>BOWMAN, B. H</au><au>FUNMEI YANG</au><au>HERBERT, D. C</au><au>WEAKER, F. J</au><au>ADRIAN, E. K</au><au>ROBINSON, L. K</au><au>WALTER, C. A</au><au>EDDY, C. A</au><au>RIEHL, R</au><au>PAUERSTEIN, C. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1990-08-05</date><risdate>1990</risdate><volume>265</volume><issue>22</issue><spage>13344</spage><epage>13350</epage><pages>13344-13350</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human
TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration.
Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding
region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes
containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing
TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher
than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels
are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration
in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload.
Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human
TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the
molecular basis of transferrin regulation throughout mammalian development into the aging process.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>2376597</pmid><doi>10.1016/S0021-9258(19)38304-8</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Base Sequence Biological and medical sciences Chimera Chloramphenicol O-Acetyltransferase - genetics Chloramphenicol O-Acetyltransferase - metabolism Female Fundamental and applied biological sciences. Psychology Gene expression Gene Expression - drug effects genes Humans Male Mice Mice, Inbred C57BL Mice, Transgenic Molecular and cellular biology Molecular genetics Molecular Sequence Data Plasmids promoters RNA, Messenger - genetics RNA, Messenger - isolation & purification Transcription, Genetic Transferrin - biosynthesis Transferrin - genetics |
title | Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice |
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