Systems genetic analysis of peripheral iron parameters in the mouse

Byron Jones, John L. Beard, Jennifer N. Gibson, Erica L. Unger, Richard P. Allen, Kristin A. McCarthy, Christopher J. Earley

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Iron homeostasis is one of the most critical functions in living systems. Too little iron can lead to anemia and tissue-specific disorders, such as splenomegaly. Excessive systemic iron is characteristic of hemochromatosis and is implicated in the brain in Parkinson's disease. With the exception of some single gene diseases like hemochromatosis, we know little about geneticbased, individual differences in iron-related parameters and their impact on biology. To model genetic control of iron homeostasis, we measured liver, spleen, and plasma iron concentrations, hematocrit and hemoglobin, transferrin saturation, and total iron-binding capacity in several BXD/Ty recombinant inbred mouse strains derived from C57BL/6 and DBA/2 progenitors. At 120 days of age, the animals were killed for iron analysis. All measures showed genetic-based variability consistent with polygenic influence. Analysis of principal components of the seven measures revealed three factors that we named availability, transport, and storage. Quantitative trait loci (QTL) analysis revealed one suggestive QTL on chromosome 5 for availability, two suggestive QTL (one on chromosome 1 and the other on chromosome 7) for transport, and one weak QTL on chromosome 2 for storage. The results show that iron homeostasis is a complex trait and is influenced by multiple genes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 1 2007

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Iron
Quantitative Trait Loci
Homeostasis
Hemochromatosis
Chromosomes, Human, Pair 5
Inbred Strains Mice
Chromosomes, Human, Pair 7
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 1
Genetic Models
Splenomegaly
Transferrin
Principal Component Analysis
Hematocrit
Individuality
Genes
Parkinson Disease
Anemia
Hemoglobins
Spleen

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Systems genetic analysis of peripheral iron parameters in the mouse. / Jones, Byron; Beard, John L.; Gibson, Jennifer N.; Unger, Erica L.; Allen, Richard P.; McCarthy, Kristin A.; Earley, Christopher J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 293, No. 1, 01.07.2007.

Research output: Contribution to journalArticle

Jones, Byron ; Beard, John L. ; Gibson, Jennifer N. ; Unger, Erica L. ; Allen, Richard P. ; McCarthy, Kristin A. ; Earley, Christopher J. / Systems genetic analysis of peripheral iron parameters in the mouse. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2007 ; Vol. 293, No. 1.
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