MURINE MODEL OF LAD II/EARLY ONSET PERIODONTITIS

LAD II/早发性牙周炎的小鼠模型

• 批准号: 2875479
• 负责人: RICHARD NIEDERMAN
• 金额: $ 6.25万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2875479
• 关键词: Actinobacillus actinomycetemcomitans; adolescence (12-20); antibacterial antibody; antibiotics; bactericidal immunity; cellular immunity; computer assisted sequence analysis; cytokine; dental disorder chemotherapy; disease /disorder etiology; disease /disorder prevention /control; enzyme linked immunosorbent assay; gene targeting; genetic susceptibility; genetically modified animals; immunocytochemistry; inflammation; laboratory mouse; leukocyte disorder; oral bacteria; pathologic process; periodontitis; polymerase chain reaction; prostaglandin E; selectins

Periodontal disease is an inflammatory infection of the periodontium which results in alveolar bone loss. Evidence from a number of laboratories indicates that the incidence of early onset periodontal disease (before age 20) is high (greater than 2 percent of the US population), and may be due to defects in leukocyte function. Of particular relevance to this application are the human leukocyte adhesion deficiencies termed LAD-II. Patients with these disorders display specific defects in the selectin ligand adhesion molecules. They also exhibit severe infections, including early onset periodontal disease. Like other forms of early onset periodontal disease, it is postulated, but not proven, that LAD is responsible for the observed aggressive periodontal disease. In the studies proposed in this application we will directly test this hypothesis. Genetically- engineered mice simultaneously deficient in two adhesion molecules (P- /E-selectin, LAD-II equivalent) will be used for these experiments. Age, gender, and strain matched wild type mice will serve as controls. Three different experimental approaches will be utilized. 1. Naturally occurring periodontal bone loss will be determined morphometrically and histologically. 2. The naturally occurring periodontal bacteria will be identified, and correlated with alveolar bone loss. 3. The correlated periodontal cellular inflammatory infiltrate and inflammatory cytokine responses will be determined. These studies will characterize the first animal model system for naturally-occurring early onset periodontal disease. They also will establish the role of the leukocyte selectin adhesion molecules in this disease. Thus, the proposed studies will provide a better understanding of periodontal disease pathogenesis, and more broadly, infectious diseases in general. They may also suggest ways to prevent their progress.

牙周病是一种牙周组织的炎症性感染 这导致牙槽骨损失。 一些证据表明， 实验室表明，早发性牙周炎的发病率 疾病（20岁之前）很高（超过美国的2%）， 人群），并且可能是由于白细胞功能的缺陷。 的 与本申请特别相关的是人白细胞 称为LAD-II的粘附缺陷。患有这些疾病的患者 在选择素配体粘附分子中显示特定缺陷。 他们还表现出严重的感染，包括早发性牙周炎， 疾病 像其他形式的早发性牙周病，它是 假设，但未证实，LAD负责观察到的 侵袭性牙周病在本文提出的研究中 应用程序，我们将直接测试这个假设。 从基因上来说- 同时缺乏两种粘附分子的工程小鼠（P- /E-选择素，LAD-II等效物）将用于这些实验。 年龄、性别和品系匹配的野生型小鼠将作为对照。 将使用三种不同的实验方法。1.自然 将通过形态测定法确定发生的牙周骨损失， 组织学上2.自然产生的牙周细菌将 识别，并与牙槽骨丢失相关。3.所述相关 牙周炎细胞浸润与炎性细胞因子 答案将被确定。 这些研究将描述第一个动物模型系统的特征， 自然发生的早发性牙周病。他们还将 建立白细胞选择素粘附分子在这一过程中的作用， 疾病 因此，拟议的研究将提供一个更好的理解 牙周病的发病机理，更广泛地说， 一般的疾病。他们还可能建议如何防止他们的 中求进工作总