Johansson Asa C M, Nakken Britt, Sundler Martin, Lindqvist Anna-Karin B, Johannesson Martina, Alarcón-Riquelme Marta, Bolstad Anne Isine, Humphreys-Beher Michael G, Jonsson Roland, Skarstein Kathrine, Holmdahl Rikard
Section for Medical Inflammation Research, University of Lund, Lund, Sweden.
Eur J Immunol. 2002 Jan;32(1):243-50. doi: 10.1002/1521-4141(200201)32:1<243::AID-IMMU243>3.0.CO;2-X.
The non-obese diabetic (NOD) mouse spontaneously develops diabetes and sialadenitis. The sialadenitis is characterized by histopathological changes in salivary glands and functional deficit similar to Sjögren's syndrome. In humans, Sjögren's syndrome could be associated with other connective tissue disorders, such as rheumatoid arthritis. In the present study the genetic control of sialadenitis in mice was compared to that of arthritis. We have previously reported a NOD locus, identified in an F2 cross with the H2(q) congenic NOD (NOD.Q) and C57BL/10.Q (B10.Q) strains, that promoted susceptibility to collagen-induced arthritis. The sialadenitis in NOD.Q showed a similar histological phenotype as in NOD, whereas no submandibular gland infiltration was found in B10.Q. The development of sialadenitis was independent of immunization with type II collagen and established arthritis. To identify the genetic control of sialadenitis, a gene segregation experiment was performed on an (NOD.QxB10.Q)F2 cross and genetic mapping of 353 F2 mice revealed one significant locus associated with sialadenitis on chromosome 4, LOD score 4.7. The NOD.Q allele-mediated susceptibility under a recessive inheritance pattern. The genetic control of sialadenitis seemed to be unique in comparison to diabetes and arthritis, as no loci associated with these diseases have been identified at the same location.
非肥胖糖尿病(NOD)小鼠会自发发展为糖尿病和涎腺炎。涎腺炎的特征是唾液腺出现组织病理学变化以及功能缺陷,类似于干燥综合征。在人类中,干燥综合征可能与其他结缔组织疾病相关,如类风湿关节炎。在本研究中,对小鼠涎腺炎的遗传控制与关节炎的遗传控制进行了比较。我们之前报道过一个NOD基因座,在与H2(q)同源基因NOD(NOD.Q)和C57BL/10.Q(B10.Q)品系的F2杂交中被鉴定出来,它促进了对胶原诱导性关节炎的易感性。NOD.Q中的涎腺炎表现出与NOD相似的组织学表型,而在B10.Q中未发现下颌下腺浸润。涎腺炎的发展与II型胶原免疫和已确立的关节炎无关。为了确定涎腺炎的遗传控制,对(NOD.QxB10.Q)F2杂交进行了基因分离实验,对353只F2小鼠的基因定位显示在4号染色体上有一个与涎腺炎相关的显著基因座,LOD分数为4.7。NOD.Q等位基因在隐性遗传模式下介导易感性。与糖尿病和关节炎相比,涎腺炎的遗传控制似乎是独特的,因为在同一位置未发现与这些疾病相关的基因座。