Human transferrin: Expression and iron modulation of chimeric genes in transgenic mice

Gwendolyn S. Adrian, Barbara H. Bowman, Damon C. Herbert, Frank J. Weaker, Erle K. Adrian, LeAnn K. Robinson, Christi A Walter, Carlton A. Eddy, Robert Riehl, Carl J. Pauerstein, Funmei Yang

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)13344-13350
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number22
StatePublished - Aug 5 1990

Fingerprint

Transferrin
Transgenic Mice
Iron
Genes
Modulation
Liver
Chloramphenicol O-Acetyltransferase
Base Pairing
Brain
5' Flanking Region
Tissue
Transgenes
Messenger RNA
Iron Overload
Protein Transport
Reporter Genes
Germ Cells
Testis
Blood Proteins
Aging of materials

ASJC Scopus subject areas

  • Biochemistry

Cite this

Adrian, G. S., Bowman, B. H., Herbert, D. C., Weaker, F. J., Adrian, E. K., Robinson, L. K., ... Yang, F. (1990). Human transferrin: Expression and iron modulation of chimeric genes in transgenic mice. Journal of Biological Chemistry, 265(22), 13344-13350.

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 journalArticle

Adrian, GS, Bowman, BH, Herbert, DC, Weaker, FJ, Adrian, EK, Robinson, LK, Walter, CA, Eddy, CA, Riehl, R, Pauerstein, CJ & Yang, F 1990, 'Human transferrin: Expression and iron modulation of chimeric genes in transgenic mice', Journal of Biological Chemistry, vol. 265, no. 22, pp. 13344-13350.
Adrian GS, Bowman BH, Herbert DC, Weaker FJ, Adrian EK, Robinson LK et al. Human transferrin: Expression and iron modulation of chimeric genes in transgenic mice. Journal of Biological Chemistry. 1990 Aug 5;265(22):13344-13350.
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. / Human transferrin : Expression and iron modulation of chimeric genes in transgenic mice. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 22. pp. 13344-13350.
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