HERITABLE DISORDERS OF CONNECTIVE TISSUE

该科继续进行研究， 结缔组织遗传性疾病的机制，特别是 成骨细胞增殖（OI）和Ehlers-Danlos（EDS），并在应用这种 治疗这些疾病的信息。 一个主要的利益 本节旨在确定OI和EDS患者的胶原突变 并确定类型和位置之间的关系， 突变和结缔组织疾病的严重程度。突变 本节和其他实验室鉴定的α 2（I）胶原蛋白链 为我们提出的区域模式提供了额外的支持。 该科的第二个主要兴趣是开发选择性反义核酸。 抑制突变型胶原等位基因作为治疗的方法 干预该小组使用了靶向突变mRNA的硫代寡核苷酸， 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， 例如核酶和载体构建体用于增加抑制 效率 感兴趣的第三个焦点是骨生物学的OI。 培养的成骨细胞用于研究骨细胞修饰和 分泌变异胶原蛋白。 在临床研究中， 激素在患有OI的矮小儿童中继续决定其对 生长刺激、骨密度和骨形态测量特性。 在OI的神经学方面的合作兴趣， 最大限度地发挥OI儿童的身体功能， 康复也在进行中。

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.