title: Systems genetic analysis of the effects of iron deficiency in mouse brain.
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.
authors.affiliation: Intercollege Graduate Degree Program in Neuroscience, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Jellen
authors.forename: Erica L
authors.initials: EL
authors.lastname: Unger
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Sarah
authors.initials: S
authors.lastname: Rousseau
authors.forename: Xusheng
authors.initials: X
authors.lastname: Wang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Earley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Allen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Miles
authors.forename: Byron C
authors.initials: BC
authors.lastname: Jones
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D000090463:Iron Deficiencies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D040641:Quantitative Trait Loci
chemical_list: D027342:Excitatory Amino Acid Transporter 2; C493396:Slc1a2 protein, mouse