Genetic analysis of iron-deficiency effects on the mouse spleen
- 6 July 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Mammalian Genome
- Vol. 22 (9-10), 556-562
- https://doi.org/10.1007/s00335-011-9344-4
Abstract
Iron homeostasis is crucial to many biological functions in nearly all organisms, with roles ranging from oxygen transport to immune function. Disruption of iron homeostasis may result in iron overload or iron deficiency. Iron deficiency may have severe consequences, including anemia or changes in immune or neurotransmitter systems. Here we report on the variability of phenotypic iron tissue loss and splenomegaly and the associated quantitative trait loci (QTLs), polymorphic areas in the mouse genome that may contain one or more genes that play a role in spleen iron concentration or spleen weight under each dietary treatment. Mice from 26 BXD/Ty recombinant inbred strains, including the parent C57BL/6 and DBA/2 strains, were randomly assigned to adequate iron or iron-deficient diets at weaning. After 120 days, splenomegaly was measured by spleen weight, and spleen iron was assessed using a modified spectrophotometry technique. QTL analyses and gene expression comparisons were then conducted using the WebQTL GeneNetwork. We observed wide, genetic-based variability in splenomegaly and spleen iron loss in BXD/Ty recombinant inbred strains fed an iron-deficient diet. Moreover, we identified several suggestive QTLs. Matching our QTLs with gene expression data from the spleen revealed candidate genes. Our work shows that individual differences in splenomegaly response to iron deficiency are influenced at least partly by genetic constitution. We propose mechanistic hypotheses by which splenomegaly may result from iron deficiency.Keywords
This publication has 18 references indexed in Scilit:
- Systems genetics can provide new insights in to immune regulation and autoimmunityJournal of Autoimmunity, 2008
- Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in miceNature Genetics, 2007
- Systems genetic analysis of peripheral iron parameters in the mouseAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
- Multiple polymorphic loci determine basal hepatic and splenic iron status in miceHepatology, 2006
- Systems Genetics: The Next Generation in Genetics Research?Published by Wiley ,2006
- On the Integration of Alcohol‐Related Quantitative Trait Loci and Gene Expression AnalysesAlcohol: Clinical and Experimental Research, 2004
- Multigenic control of hepatic iron loading in a murine model of hemochromatosisGastroenterology, 2004
- Pre- and Postweaning Iron Deficiency Alters Myelination in Sprague-Dawley RatsDevelopmental Neuroscience, 2003
- Effects of HFE C282Y and H63D Polymorphisms and Polygenic Background on Iron Stores in a Large Community Sample of TwinsAmerican Journal of Human Genetics, 2000
- The effects of iron deficiency and iron overload on cell-mediated immunity in the mouseBritish Journal of Nutrition, 1994