This Core resource to a program-project is focused on defining inborn protein defects that causeosteochondrodysplasia syndromes. We are determining the protein consequences at the molecular level ofmutations in genes that cause defects in cartilage structure. This Protein Biochemistry Core activelycollaborates in parallel with all projects by providing analytical data from specialized methods, includingprotein mass spectrometry, applied to tissue samples, purified proteins and cell-culture products. Bothluman material from the International Skeletal Dysplasias Registry and mouse tissue and cellular productsrom genetically engineered transgenic strains are being studied. Hypotheses as to the nature andbiochemical effects of mutations that cause abnormal skeletal development and adult function are integral tothe overall goals and aims of all projects and cores. The focus of the Protein Biochemistry Core is tounderstand the downstream molecular effects of mutations, both new ones identified by human genetic inkage and mutational analysis, and established mutations still with key questions on their proteinpathogenesis and created transgenic defects in mice. An example of the latter is the systemic collagendefect in crtap -/- mice.The clinical significance of core work includes direct benefits to families with the conditions under studythrough more specific diagnoses. In the long term, through an understanding of the effects of altered geneexpression, rational approaches to therapy are possible.
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