title: Identification of gene regions regulating inflammatory microglial response in the rat CNS after nerve injury.
abstract: Local CNS inflammation takes place in many neurological disorders and is important for autoimmune neuroinflammation. Microglial activation is strain-dependent in rats and differential MHC class II expression is influenced by variations in the Mhc2ta gene. Despite sharing Mhc2ta and MHC class II alleles, BN and LEW.1N rats differ in MHC class II expression after ventral root avulsion (VRA). We studied MHC class II expression and glial activation markers in BN rats after VRA. Our results demonstrate that MHC class II expression originates from a subpopulation of IBA1(+), ED1(-), and ED2(-) microglia. We subsequently performed a genome-wide linkage scan in an F2(BNxLEW.1N) population, to investigate gene regions regulating this inflammatory response. Alongside MHC class II, we studied the expression of MHC class I, co-stimulatory molecules, complement components, microglial markers and Il1b. MHC class II and other transcripts were commonly regulated by gene regions on chromosomes 1 and 7. Furthermore, a common region on chromosome 10 regulated expression of complement and co-stimulatory molecules, while a region on chromosome 11 regulated MHC class I. We also detected epistatic interactions in the regulation of the inflammatory process. These results reveal the complex regulation of CNS inflammation by several gene regions, which may have relevance for disease.
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, S171 76 Stockholm, Sweden. Margarita.Diez@ki.se
authors.forename: Margarita
authors.initials: M
authors.lastname: Diez
authors.forename: Nada
authors.initials: N
authors.lastname: Abdelmagid
authors.forename: Karin
authors.initials: K
authors.lastname: Harnesk
authors.forename: Mikael
authors.initials: M
authors.lastname: Ström
authors.forename: Olle
authors.initials: O
authors.lastname: Lidman
authors.forename: Maria
authors.initials: M
authors.lastname: Swanberg
authors.forename: Rickard
authors.initials: R
authors.lastname: Lindblom
authors.forename: Faiez
authors.initials: F
authors.lastname: Al-Nimer
authors.forename: Maja
authors.initials: M
authors.lastname: Jagodic
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D002874:Chromosome Mapping; D004660:Encephalitis / Q000276:immunology*; D004843:Epistasis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D017628:Microglia / Q000502:physiology*; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C045084:invariant chain