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 TF 5′-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, ≧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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 13344-13350 |
| Number of pages | 7 |
| Journal | Journal of Biological Chemistry |
| Volume | 265 |
| Issue number | 22 |
| State | Published - Aug 5 1990 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Human transferrin : Expression and iron modulation of chimeric genes in transgenic mice. / Adrian, Gwendolyn S.; Bowman, Barbara H.; Herbert, Damon C.; Weaker, Frank J.; Adrian, Erle K.; Robinson, LeAnn K.; Walter, Christi A; Eddy, Carlton A.; Riehl, Robert; Pauerstein, Carl J.; Yang, Funmei.
In: Journal of Biological Chemistry, Vol. 265, No. 22, 05.08.1990, p. 13344-13350.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human transferrin
T2 - Expression and iron modulation of chimeric genes in transgenic mice
AU - Adrian, Gwendolyn S.
AU - Bowman, Barbara H.
AU - Herbert, Damon C.
AU - Weaker, Frank J.
AU - Adrian, Erle K.
AU - Robinson, LeAnn K.
AU - Walter, Christi A
AU - Eddy, Carlton A.
AU - Riehl, Robert
AU - Pauerstein, Carl J.
AU - Yang, Funmei
PY - 1990/8/5
Y1 - 1990/8/5
N2 - 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 TF 5′-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, ≧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.
AB - 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 TF 5′-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, ≧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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0025356256&partnerID=8YFLogxK
M3 - Article
C2 - 2376597
AN - SCOPUS:0025356256
VL - 265
SP - 13344
EP - 13350
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 22
ER -