title: Identification of quantitative trait loci for murine autoimmune pancreatitis.
abstract: OBJECTIVE
  Autoimmune pancreatitis (AIP) represents a rare but clinically relevant cause of pancreatic inflammation. Using MRL/Mp mice as a model of spontaneous AIP, the genetic basis of the disease was studied.
  
  
  METHODS
  To identify quantitative trait loci (QTL) of AIP, an advanced intercross line was studied, originating from MRL/MpJ parental mice and the following three mouse strains: Cast (healthy controls), BXD2 (susceptible to collagen induced arthritis), and NZM (a model of lupus erythematosus). This concept was chosen to identify both general autoimmune disease associated loci and AIP specific QTL. Therefore, generation G4 of outbred intercross mice was characterised phenotypically by scoring histopathological changes of the pancreas and genotyped with single nucleotide polymorphism (SNP) arrays. Data were analysed with the R implementation of HAPPY.
  
  
  RESULTS
  Five QTLs, correlating with the severity of AIP, were identified. Two of them mapped to chromosome 4 and one to chromosomes 2, 5, and 6, respectively. The QTL on chromosome 6 displays the highest LOD score (5.4) and contains the C-type lectin domain family 4 member a2 in its peak region, which encodes a receptor protein of dendritic cells that has previously been implicated in autoimmune diseases such as Sjogren's syndrome. AIP candidate genes of other QTL's include heterogeneous nuclear ribonucleoprotein A3; nuclear factor, erythroid derived 2, like 2; Sjogren syndrome antigen B; and ubiquitin protein ligase E3 component n-recognin 3.
  
  
  CONCLUSIONS
  This study has identified QTLs and putative candidate genes of murine AIP. Their functional role and relevance to human AIP will be studied further.
authors.affiliation: Department of Medicine II, Division of Gastroenterology, University of Rostock, E.-Heydemann-Strasse 6, Rostock, Germany.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Asghari
authors.forename: Brit
authors.initials: B
authors.lastname: Fitzner
authors.forename: Stephanie-Anna
authors.initials: SA
authors.lastname: Holzhüter
authors.forename: Horst
authors.initials: H
authors.lastname: Nizze
authors.forename: Andreia
authors.initials: A
authors.lastname: de Castro Marques
authors.forename: Susen
authors.initials: S
authors.lastname: Müller
authors.forename: Steffen
authors.initials: S
authors.lastname: Möller
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
authors.forename: Robert
authors.initials: R
authors.lastname: Jaster
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology; D003433:Crosses, Genetic; D005260:Female; D056726:Genetic Association Studies; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000235:genetics*; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*