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Byron C Jones"Genetics of Brain Iron Regulation"

Abstract :

Iron regulation in brain and in the periphery shows large inter-individual differences in humans.
Some of these differences are related to specific diseases such as hemochromatosis and some neurodegenerative diseases. Much of the individual differences can be tied to the genetic makeup of the individual and this genetically-based differential regulation can be modeled in genetic reference populations of rodents. The work in our laboratory centers on iron regulation in the brain and our animal model consists of the 25+ BXD/Ty recombinant inbred mouse strains. By studying naturally occurring variation in iron phenotypes, such as tissue iron concentration, we can tie that variability to one or more genes by way of quantitative trait loci (QTL) analysis (genetics) and how these genes respond by way of expression, to an environmental challenge such as low iron diet (genomics). We have identified several suggestive QTL related to ventral midbrain iron content, including one in the vicinity of hepcidin, a known iron management protein. Moreover, we can conduct genetic correlational analysis between our phenotypes and others measured by ourselves or by others. Thus we observe significant correlations between ventral midbrain iron content and density of dopamine receptors, dopamine receptor gene expression. By coupling QTL analysis with gene expression analysis, we can nominate candidate genes involved in brain iron management. One such example is our identification of a QTL on mouse chromosome 17 that correlates with ventral midbrain iron and also copper and zinc in other brain areas. A homologous area on human chromosome 6 has also been implicated in iron regulation and restless legs syndrome and periodic limb movements, both dopamine based disorders. Supported in part by USPHS Grant AG 021190.

Selected publications

Bianco LE, Wiesinger J, Earley CJ, Jones BC, Beard JL.
Iron deficiency alters dopamine uptake and response to L-DOPA injection in Sprague-Dawley rats.
J Neurochem. 2008 Jul;106(1):205-15. 2008 Jul 1.
Jones LC, Beard JL, Jones BC.
Genetic analysis reveals polygenic influences on iron, copper, and zinc in mouse hippocampus with neurobiological implications.
Hippocampus. 2008;18(4):398-410.
Unger EL, Beard JL, Jones BC.
Iron regulation in C57BLI6 and DBA/2 mice subjected to iron overload.
Nutr Neurosci. 2007 Feb-Apr;10(1-2):89-95.

Pierre Mormède