MOLECULAR MECHANISMS OF SKELETOGENESIS

描述：(改编自调查人员摘要)这项拨款申请 旨在研究疾病表型的起源 在转基因小鼠中表达突变的X型胶原蛋白 他们正常的内源性X型胶原蛋白。特别值得关注的是 突变的胶原分子是否会损害正常人的功能 分子通过参与异型胶原单体和 在生长板内的后续网络， 或者突变分子是否可能独立地影响 生长板软骨细胞的功能(功能表型的增加)。 这项工作可以分为5个具体目标：1)论证 突变的和正常的胶原分子是共表达的，并且可以相互作用 在体内；2)检测转基因表型在小鼠体内的作用 内源性X型胶原表达缺失；3)测定 转基因表达对生长板软骨细胞增殖的影响 肥大与细胞凋亡；4)确定转基因表达 影响其他生长板大分子的合成；以及5) 确定转基因表达对骨形成的影响， 再吸收作用和矿物结构。

DESCRIPTION: (Adapted from investigator's abstract) This grant request is designed to study the origin of the disease phenotype that develops in transgenic mice expressing a mutant type X collagen in addition to their normal endogenous type X collagen. Of particular interest is whether the mutant collagen molecules impair the function of the normal molecules via their participation in heterotypic collagen monomers and subsequent network within the growth plate, or whether the mutant molecules may independently affect the function of the growth plate chondrocytes (a gain of function phenotype). The work can be divided into 5 Specific Aims: 1) demonstrating that the mutant and normal collagen molecules are co-expressed and can interact in vivo; 2) determining the effect of the transgene phenotype in the absence of endogenous type X collagen expression; 3) determining the effect of transgene expression on growth plate chondrocyte proliferation, hypertrophy and apoptosis; 4) determining whether transgene expression affects the synthesis of other growth plate macromolecules; and 5) determining the effect of transgene expression on bone formation, resorption and mineral structure.