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Candidate chromosome 1 disease susceptibility genes for Sjogren's syndrome xerostomia are narrowed by novel NOD.B10 congenic mice. - PubMed - NCBI
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Clin Immunol. 2014 Jul;153(1):79-90. doi: 10.1016/j.clim.2014.03.012. Epub 2014 Mar 29.

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

Author information

1
The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA. Electronic address: pmongini@nshs.edu.
2
The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA. Electronic address: jkramer@buffalo.edu.
3
David Geffen School of Medicine at UCLA, 341 Boyer Hall (MBI), 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA. Electronic address: tishikaw@xf7.so-net.ne.jp.
4
David Geffen School of Medicine at UCLA, 341 Boyer Hall (MBI), 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA. Electronic address: HHerschman@mednet.ucla.edu.
5
Charles River Laboratories, Genetic Testing Services, 185 Jordan Road, Troy, NY 12180, USA. Electronic address: Donna.Esposito@crl.com.

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

PMID:
24685748
PMCID:
PMC4058348
DOI:
10.1016/j.clim.2014.03.012
[Indexed for MEDLINE]
Free PMC Article
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