CREATION OF THE AD02 MOUSE

描述（由申请人提供）：常染色体显性遗传性石骨症2型（ADO2）是一种骨质疏松症，由骨吸收受损引起。这种疾病通常由氯离子通道7基因（CLCN 7）的错义突变引起。疾病的严重程度差异很大，即使在同一个家庭的成员之间，三分之一的突变个体是无症状携带者。我们实验室的体外研究表明，无症状携带者的破骨细胞正常吸收骨，而受影响的个体的破骨细胞有明显的骨吸收缺陷。因此，受影响的个人和运营商之间的差异是由于破骨细胞的具体属性。我们的初步数据，是一致的，有一个以上的修饰基因是负责这种差异。本提案的重点是创建ADO2小鼠模型。这种动物模型将使我们能够测试潜在的治疗方法，并找到控制疾病严重程度的基因。摘要：常染色体显性遗传性石骨症（ADO2）是一种骨密度高，但骨质脆弱的疾病。疾病的严重程度在携带者（无疾病）和严重受影响的个体之间存在差异，严重受影响的个体有多处骨折，骨感染，偶尔失明。本提案的重点是创建ADO2小鼠模型。这种动物模型将使我们能够测试潜在的治疗方法，并找到控制疾病严重程度的基因。

DESCRIPTION (provided by applicant): Autosomal dominant osteopetrosis, type 2 (ADO2) is an osteosclerotic disorder that results from impaired osteoclastic bone resorption. The disorder usually results from missense mutations in the Chloride Channel 7 gene (CLCN7). Disease severity varies widely, even among members of the same family, and one third of individuals with mutations are asymptomatic carriers. In vitro studies in our laboratory indicate that osteoclasts from asymptomatic carriers resorb bone normally, while those from affected individuals have markedly defective bone resorption. Thus, the difference between affected individuals and carriers is due to osteoclast specific properties. Our preliminary data, are consistent with there being more than one modifier gene that is responsible for this difference. This proposal focuses on the creation of an ADO2 mouse model. This animal model will allow us to test potential therapies and find genes that control disease severity. Lay abstract: Autosomal dominant osteopetrosis (ADO2) is a disease in which there is dense, but fragile bone. The severity of the disease varies between carriers (who are disease free) and severely affected individuals, who have multiple fractures, bone infections and, occasionally, blindness. This proposal focuses on the creation of an ADO2 mouse model. This animal model will allow us to test potential therapies and find genes that control disease severity.