title: The calcitonin receptor gene is a candidate for regulation of susceptibility to herpes simplex type 1 neuronal infection leading to encephalitis in rat.
abstract: Herpes simplex encephalitis (HSE) is a fatal infection of the central nervous system (CNS) predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s) regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL), Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5) governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr) as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.
authors: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. nada.abdelmagid@ki.se
authors: Nada
authors: N
authors: Abdelmagid
authors: Biborka
authors: B
authors: Bereczky-Veress
authors: André Ortlieb
authors: AO
authors: Guerreiro-Cacais
authors: Petra
authors: P
authors: Bergman
authors: Katarina M
authors: KM
authors: Luhr
authors: Tomas
authors: T
authors: Bergström
authors: Birgit
authors: B
authors: Sköldenberg
authors: Fredrik
authors: F
authors: Piehl
authors: Tomas
authors: T
authors: Olsson
authors: Margarita
authors: M
authors: Diez
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D020803:Encephalitis, Herpes Simplex / Q000235:genetics*; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D018259:Herpesvirus 1, Human; D009474:Neurons / Q000821:virology*; D040641:Quantitative Trait Loci; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D018003:Receptors, Calcitonin / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D018003:Receptors, Calcitonin