Candidate chromosome 1 disease susceptibility genes for Sjogren's syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

Clin Immunol. 2014 Jul;153(1):79-90. doi: 10.1016/j.clim.2014.03.012. Epub 2014 Mar 29.

Abstract

Sjogren's syndrome (SS) is characterized by salivary gland leukocytic infiltrates and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1 within the span of the Aec2 region. In an attempt to demonstrate that COX-2 drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox-2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking genes failed manifest xerostomia. Further backcrossing yielded disease-susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that critical Aec2 genes lie within a 1.56 to 2.17Mb span of DNA downstream of Cox-2. Bioinformatics analysis revealed that susceptible and non-susceptible lines exhibit non-synonymous coding SNPs in 8 protein-encoding genes of this region, thereby better delineating candidate Aec2 alleles needed for SS xerostomia.

Keywords: B lymphocytes; Cyclooxygenase-2; Genetic susceptibility; NOD mice; Sjogren's syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping
  • Chromosomes, Mammalian*
  • Cyclooxygenase 2 / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Mice
  • Mice, Congenic
  • Mice, Inbred NOD
  • Open Reading Frames
  • Recombination, Genetic
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • Sialadenitis / genetics
  • Sialadenitis / immunology
  • Sialadenitis / pathology
  • Sjogren's Syndrome / complications*
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / immunology
  • Xerostomia / etiology*

Substances

  • Cyclooxygenase 2