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 这一信息有助于这些疾病的治疗。 该部分的一个主要兴趣是确定胶原突变 在OI和EDS患者中并确定两者之间的关系 突变的类型和位置以及连接的严重程度 组织紊乱。α2(I)胶原链突变的鉴定 本部分和其他实验为 我们已经提出了区域模式。 该科的第二个主要兴趣是制定有选择性的 反义抑制突变的胶原等位基因作为一种治疗方法 治疗性干预。我们已经使用了针对突变的mrna的硫代寡核苷酸。 1例慢性萎缩性胃炎患者成纤维细胞中的核糖核酸 IV OI类。我们已经实现了对突变等位基因的选择性抑制 并正在寻求核酶和载体构建等方法来 提高抑制效率。 我们一直在开发的第三个兴趣焦点是骨骼 OI的生物学。我们正在使用培养的成骨细胞来研究骨骼的方式 细胞修饰和分泌突变的胶原蛋白。我们还在追求 继发性OI基质非胶原性异常。 在临床研究中，我们正在继续我们的生长治疗试验。 OI矮小儿童体内激素对生长发育的影响 刺激、骨密度和骨形态计量学特性。我们是 继续我们在OI的神经学方面的合作兴趣 在最大化OI儿童的身体功能方面， 积极的康复。

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 the 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 relationship 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. We have used thio oligos targeted to mutant mRNA nd nuclear RNA in the cultured fibroblasts of a patient with type IV OI. We have achieved selective suppression of the mutant allele and are pursuing approaches such as ribozymes and vector constructs to increase suppression efficiency. A third focus of interest which we have been developing is in the bone biology of OI. We are using cultured osteoblasts to study the way bone cells modify and secrete mutant collagen. We are also pursing the secondary non-collagenous abnormalities of OI matrix. In clinical studies, we are continuing our treatment trial of growth hormone in short children with OI to determine its effects on growth stimulation, bone density and bone morphometric properties. We are continuing our collaborative interests in the neurological aspects of OI and in maximizing the physical functioning of OI children though aggressive rehabilitation.