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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
Main Authors: 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
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cited_by cdi_FETCH-LOGICAL-c441t-5ea9d5b7d12595152d0b2d0745048eff6647561b4fe0d8c8dad35ae5e5bb1fe03
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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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identifier ISSN: 0021-9258
ispartof The Journal of biological chemistry, 1990-08, Vol.265 (22), p.13344-13350
issn 0021-9258
1083-351X
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source ScienceDirect Journals
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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