Systems genetic analysis of the effects of iron deficiency in mouse brain

Leslie C. Jellen, Erica L. Unger, Lu Lu, Robert W. Williams, Sarah Rousseau, Xusheng Wang, Christopher J. Earley, Richard P. Allen, Michael F. Miles, Byron C. Jones

Research output: Contribution to journalArticle

Abstract

Iron regulation in the brain is both necessary and highly complex. Too little or too much iron can compromise neurological function, yet we still do not know all of the regulatory processes. In our research, we seek to identify genes and gene networks underlying individual differences in brain iron regulation. To this end, we fed mice from 20+ inbred strains a diet low in iron from weaning to 4 months of age. At sacrifice, we measured iron content in the ventral midbrain (VMB). The VMB contains the substantia nigra, a region particularly vulnerable to iron imbalance. The results showed high, inter-strain variability in dietary iron reduction, from almost no loss to more than 40 % vs. control. When we performed quantitative trait loci (QTL) analysis, we observed a significant area on chromosome 2. Within this QTL, we selected glial high-affinity glutamate transporter 1 (Glt1) as the leading candidate. Expression of this gene is both correlated with VMB iron and is also cis-modulated by local sequence variants that segregate in the BXD family. VMB expression differences of Glt1 in six strains covary with differential susceptibility to VMB iron loss.

Original languageEnglish (US)
Pages (from-to)147-157
Number of pages11
JournalNeurogenetics
Volume13
Issue number2
DOIs
StatePublished - May 1 2012

Keywords

  • BXD
  • Glial glutamate high-affinity transporter
  • Quantitative trait loci
  • Recombinant inbred
  • Ventral midbrain

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience

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  • Cite this

    Jellen, L. C., Unger, E. L., Lu, L., Williams, R. W., Rousseau, S., Wang, X., Earley, C. J., Allen, R. P., Miles, M. F., & Jones, B. C. (2012). Systems genetic analysis of the effects of iron deficiency in mouse brain. Neurogenetics, 13(2), 147-157. https://doi.org/10.1007/s10048-012-0321-1