GENETICS OF BACTERIALLY-INDUCED ALVEOLAR BONE LOSS

细菌引起的牙槽骨丢失的遗传学

• 批准号: 6379755
• 负责人: PAMELA J BAKER
• 金额: $ 31.85万
• 依托单位: BATES COLLEGE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379755
• 关键词: Bacteroides gingivalis; bactericidal immunity; biomarker; disease /disorder model; gene targeting; genetic mapping; genetic strain; genetic susceptibility; genetically modified animals; graft versus host disease; host organism interaction; laboratory mouse; oral bacteria; pathologic bone resorption; pathologic process; phenotype; quantitative trait loci

DESCRIPTION (adapted from the Investigator's abstract): Periodontal disease among adult humans is a significant public health burden. It is strongly associated with the gram-negative bacterium, Porphyromonas gingivalis, yet bacteria alone do not explain population variance in the disease. There is a notable genetic component to both disease incidence and severity. Mouse models have proven extremely valuable in dissecting the pathobiology of various diseases. Modern molecular genetics, including quantitative trait locus (QTL) analysis, is a powerful tool for unraveling the genetic polymorphisms underlying various diseases in the mouse, including susceptibility and resistance to infectious diseases. Large portions of the murine genome are shared with the human genome, so that identification and localization of murine loci have facilitated discovery of their human counterparts. During the current support period, the Principal Investigator has developed a mouse model in which alveolar bone loss is reliably induced in mice by oral infection with P. gingivalis. In collaboration with Dr. Derry Roopenian of The Jackson Laboratory, knockout mice with various discrete immunodeficiencies have been used to identify several factors that contribute to bone loss. The Principal Investigator has also found that different strains of immunocompetent mice differ in their susceptibility to bone loss after oral infection. Through F1 crosses and backcross of these mice, we have initial evidence that susceptibility and resistance to P. gingivalis- induced alveolar bone loss are heritable traits. It is proposed to study the genetic basis for this susceptibility and resistance. First, the pathophysiological processes that coincide with bone loss in this mouse model will be further characterized and other phenotypic biomarkers will be developed that correlate with bone loss. Second, QTL analysis will then be used to identify chromosomal regions associated with susceptibility and resistance. Together these aims will provide a fuller description of the pathobiology of P. gingivalis-induced alveolar bone loss and will allow the Principal Investigator to map loci and alleles involved in susceptibility and resistance. Mouse strains developed in this investigation will be available for others to study. Knowledge of the genetics gained here has a high likelihood of contributing to the identification of candidate genes in humans.

描述（改编自研究者摘要）：牙周病 是一个重大的公共卫生负担。强烈 与革兰氏阴性菌牙龈卟啉单胞菌有关， 细菌本身不能解释疾病的群体差异。有一个 显著的遗传成分对疾病的发病率和严重程度都有影响。小鼠模型 已经证明在解剖各种疾病的病理学方面非常有价值， 疾病现代分子遗传学，包括数量性状基因座（QTL） 分析，是一个强大的工具，解开遗传多态性 小鼠的各种潜在疾病，包括易感性和 抵抗传染病。鼠基因组的大部分是 与人类基因组共享，因此， 基因座促进了它们的人类对应物的发现。于本 在支持期间，主要研究者开发了一种小鼠模型， 小鼠口腔感染P. 牙龈炎与杰克逊酒店的德里鲁普尼安博士合作 实验室，基因敲除小鼠与各种离散的免疫缺陷已经 用于确定导致骨丢失的几个因素。校长 研究人员还发现，不同品系的免疫活性小鼠 在口腔感染后对骨质流失的敏感性方面存在差异。通过F1 通过这些小鼠的杂交和回交，我们有初步证据表明， 对牙龈卟啉单胞菌引起牙槽骨丢失的敏感性和抵抗性是 遗传特征建议研究其遗传基础 易感性和抗性。首先，病理生理过程， 将进一步表征与该小鼠模型中的骨丢失一致， 将开发与骨丢失相关的其它表型生物标志物。 其次，QTL分析将用于确定染色体区域 与易感性和耐药性有关。这些目标将提供 牙龈卟啉单胞菌诱导牙槽骨的病理生物学的更全面的描述 损失，并将允许主要研究者映射基因座和等位基因涉及 在易感性和抵抗力方面。本研究中开发的小鼠品系 将可供其他人研究。在这里获得的遗传学知识 有很高的可能性有助于候选基因的鉴定 在人类身上。