Submitted on August 25, 2006
Accepted on April 25, 2007
SYSTEMS GENETIC ANALYSIS OF PERIPHERAL IRON PARAMETERS IN THE MOUSE
Byron C Jones1*, John L Beard2, Jennifer N Gibson3, Erica L. Unger4, Richard P. Allen5, Kristin A. McCarthy6, and Christopher J Earley5
1 Biobehavioral Health, Penn State University, University Park, Pennsylvania, United States
2 Nutrition, Penn State University, United States
3 University Park, Pennsylvania, United States; Biobehavioral Health, Penn State University, University Park, Pennsylvania, United States
4 University Park, Pennsylvania, United States; Nutrition, Penn State University, University Park, Pennsylvania, United States
5 Neurology, Johns Hopkins Medical Institutes, Baltimore, Maryland, United States
6 Oregon Health and Science University, Portland, Oregon, United States
* To whom correspondence should be addressed. E-mail: bcj1{at}psu.edu.
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 genetic-based, individual differences in iron-related parameters and their impact on biology. In order to model genetic control of iron homeostasis, we measured liver, spleen and plasma iron concentrations, hematocrit and hemoglobin, transferrin saturation (TFS) and total iron binding capacity (TIBC) in several BXD/Ty recombinant inbred mouse strains derived from C57BL/6 and DBA/2 progenitors. At 120 days of age, the animals were sacrificed for iron analysis. All measures showed genetic-based variability, consistent with polygenic influence. Principal components analysis of the 7 measures revealed 3 factors that we named, availability, transport and storage. Quantitative trait locus (QTL) analysis revealed 1 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.
