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

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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

Fingerprint

Iron
Mesencephalon
Brain
Amino Acid Transport System X-AG
Quantitative Trait Loci
Dietary Iron
Inbred Strains Mice
Chromosomes, Human, Pair 2
Gene Regulatory Networks
Substantia Nigra
Weaning
Individuality
Neuroglia
Diet
Gene Expression
Research
Genes

All Science Journal Classification (ASJC) codes

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

Cite this

Systems genetic analysis of the effects of iron deficiency in mouse brain. / Jellen, Leslie C.; Unger, Erica L.; Lu, Lu; Williams, Robert; Rousseau, Sarah; Wang, Xusheng; Earley, Christopher J.; Allen, Richard P.; Miles, Michael F.; Jones, Byron.

In: Neurogenetics, Vol. 13, No. 2, 01.05.2012, p. 147-157.

Research output: Contribution to journalArticle

Jellen, LC, Unger, EL, Lu, L, Williams, R, Rousseau, S, Wang, X, Earley, CJ, Allen, RP, Miles, MF & Jones, B 2012, 'Systems genetic analysis of the effects of iron deficiency in mouse brain', Neurogenetics, vol. 13, no. 2, pp. 147-157. https://doi.org/10.1007/s10048-012-0321-1
Jellen, Leslie C. ; Unger, Erica L. ; Lu, Lu ; Williams, Robert ; Rousseau, Sarah ; Wang, Xusheng ; Earley, Christopher J. ; Allen, Richard P. ; Miles, Michael F. ; Jones, Byron. / Systems genetic analysis of the effects of iron deficiency in mouse brain. In: Neurogenetics. 2012 ; Vol. 13, No. 2. pp. 147-157.
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