The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA.
David Geffen School of Medicine at UCLA, 341 Boyer Hall (MBI), 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
Clin Immunol. 2014 Jul;153(1):79-90. doi: 10.1016/j.clim.2014.03.012. Epub 2014 Mar 29.
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.
干燥综合征(SS)的特征是唾液腺白细胞浸润和唾液分泌减少(口干)。Cox-2(Ptgs2)位于染色体 1 上的 Aec2 区域内。为了证明 COX-2 驱动抗体依赖性低分泌,生成了携带 Cox-2 基因的 NOD.B10 同基因小鼠。具有 Cox-2 侧翼基因非-NOD 等位基因的同基因系没有表现出口干。进一步的回交产生了易感的 NOD.B10 Cox-2flox 系;精细遗传图谱确定,关键的 Aec2 基因位于 Cox-2 下游的 DNA 1.56 至 2.17Mb 范围内。生物信息学分析表明,易感和非易感系在该区域的 8 个蛋白编码基因中表现出非同义编码 SNP,从而更好地描绘了 SS 口干所需的候选 Aec2 等位基因。