Expression of a human chimeric transferrin gene in senescent transgenic mice reflects the decrease of transferrin levels in aging humans

Gwendolyn S. Adrian, Damon C. Herbert, Le Ann K. Robinson, Christi A. Walter, James M. Buchanan, Erle K. Adrian, Frank J. Weaker, Carlton A. Eddy, Funmei Yang, Barbara H. Bowman

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Transgenic mice provide a means to study human gene expression in vivo throughout the aging process. A DNA sequence containing 668 bp of the 5′ regulatory region of the human transferrin gene was fused to the bacterial reporter gene chloramphenicol acetyl transferase (TF-CAT) and introduced into the mouse genome. Expression of the human chimeric transferrin gene was similar to the tissue patterns of mouse and human transferrin. In aging transgenic mice, expression of the human chimeric transferrin gene was found to diminish 40% in livers between 18 and 26 months of age. Transferrin levels and serum iron levels in aging humans also diminish, as observed from measurements of total iron binding capacity and percent iron saturation in sera from 701 individuals ranging from 0 to 99 years of age. In contrast, in transgenic mice and nontransgenic mice, the mouse endogenous plasma transferrin and endogenous Tf mRNA increase significantly during aging. Neither the decrease of human TF-CAT nor the increase of mouse transferrin during aging appears to be part of a typical inflammatory reaction. Although the 5′ regions of the human transferrin and mouse transferrin genes are homologous, sequence diversities exist which could account for the different responses to inflammation and aging observed.

Original languageEnglish (US)
Pages (from-to)168-176
Number of pages9
JournalBBA - Gene Structure and Expression
Volume1132
Issue number2
DOIs
StatePublished - Sep 24 1992

Keywords

  • Acute phase reaction
  • Aging
  • Albumin
  • C3
  • Serum amyloid protein
  • Total iron binding capacity
  • Transferrin
  • Transgenic mice

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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    Adrian, G. S., Herbert, D. C., Robinson, L. A. K., Walter, C. A., Buchanan, J. M., Adrian, E. K., Weaker, F. J., Eddy, C. A., Yang, F., & Bowman, B. H. (1992). Expression of a human chimeric transferrin gene in senescent transgenic mice reflects the decrease of transferrin levels in aging humans. BBA - Gene Structure and Expression, 1132(2), 168-176. https://doi.org/10.1016/0167-4781(92)90008-N