title: Candidate chromosome 1 disease susceptibility genes for Sjogren's syndrome xerostomia are narrowed by novel NOD.B10 congenic mice.
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.
authors.affiliation: 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.
authors.forename: Patricia K A
authors.initials: PK
authors.lastname: Mongini
authors.affiliation: 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.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Kramer
authors.affiliation: 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.
authors.forename: Tomo-O
authors.initials: TO
authors.lastname: Ishikawa
authors.affiliation: 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.
authors.forename: Harvey
authors.initials: H
authors.lastname: Herschman
authors.affiliation: Charles River Laboratories, Genetic Testing Services, 185 Jordan Road, Troy, NY 12180, USA. Electronic address: Donna.Esposito@crl.com.
authors.forename: Donna
authors.initials: D
authors.lastname: Esposito
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D051546:Cyclooxygenase 2 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D016366:Open Reading Frames; D011995:Recombination, Genetic; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D012793:Sialadenitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D014987:Xerostomia / Q000209:etiology*
chemical_list: D051546:Cyclooxygenase 2
keywords: B lymphocytes; Cyclooxygenase-2; Genetic susceptibility; NOD mice; Sjogren's syndrome