HERITABLE DISORDERS OF CONNECTIVE TISSUE

该科继续进行旨在阐明分子的研究。 结缔组织遗传性疾病的机制，特别是 成骨不全(OI)和Ehler-Danlos(EDS)及其应用 这些疾病的治疗信息。美国政府的一个主要利益 切片鉴定OI和EDS患者的胶原突变 并确定其类型和位置之间的关系 突变和结缔组织疾病的严重程度。基因突变 本部分和其他实验室鉴定的α2(I)胶原链 为我们提出的区域模式提供了额外的支持。 该部门的第二个主要兴趣是发展选择性反义 抑制突变的胶原等位基因作为一种治疗方法 干预。该研究小组使用了针对突变mRNA的硫代寡核苷酸 一例IV型OI患者培养的成纤维细胞中的核RNA。 选择性抑制突变等位基因，并正在寻求方法 例如核酶和载体构建物用来增加抑制 效率。第三个感兴趣的焦点是OI的骨生物学。 培养的成骨细胞被用来研究骨细胞修改和 分泌突变的胶原蛋白。在临床研究中，对生长发育的治疗试验 患有OI的矮小儿童中的激素继续决定其对 生长刺激、骨密度和骨形态计量学特性。 OI和In的神经学方面的合作兴趣 尽管具有攻击性，但使OI儿童的身体功能最大化 康复工作也在进行中。

The Section has continued its studies aimed at elucidating the molecular mechanisms of heritable disorders of connective tissue, specifically osteogenesis imperfecta (OI) and Ehlers-Danlos (EDS), and at applying this information to treatment of these disorders. One primary interest of the Section is to identify the collagen mutations in patients with OI and EDS and determine the relation-ship between the type and location of the mutation and the severity of the connective tissue disorder. Mutations in the alpha2(I) collagen chain identified by this Section and other labs have provided additional support for the regional model we have proposed. A second primary interest of the Section is to develop selective antisense suppression of the mutant collagen allele as an approach for therapeutic intervention. This group has used thio oligos targeted to mutant mRNA and nuclear RNA in the cultured fibroblasts of a patient with type IV OI. Selective suppression of the mutant allele and are pursuing approaches such as ribozymes and vector constructs was used to increase suppression efficiency. A third focus of interest is in the bone biology of OI. Cultured osteoblasts are used to study the way bone cells modify and secrete mutant collagen. In clinical studies, a treatment trial of growth hormone in short children with OI continues to determine its effects on growth stimulation, bone density and bone morphometric properties. Collaborative interests in the neurological aspects of OI and in maximizing the physical functioning of OI children though aggressive rehabilitation are also pursued.