Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Med Genet. 2011 Aug;48(8):557-62. doi: 10.1136/jmg.2011.089730. Epub 2011 Jun 27.

Identification of quantitative trait loci for murine autoimmune pancreatitis.

Author information

  • 1Department of Medicine II, Division of Gastroenterology, University of Rostock, E.-Heydemann-Strasse 6, Rostock, Germany.

Abstract

BACKGROUND AND AIMS:

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.

PMID:
21709168
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk