The zebrafish mutant droog as a model for human osteoporosis

斑马鱼突变体 droog 作为人类骨质疏松症模型

基本信息

批准号：
8774474
负责人：
PAMELA C YELICK
金额：
$ 21.78万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8774474
关键词：
Adult Adverse effects Affect Age Alleles Animal Model Bone Density Bone Development Bone Diseases Candidate Disease Gene Cell Culture Techniques Cells Chemicals Defect Development Diabetes Mellitus Diet Differentiation Antigens Disease Exhibits Fracture Gene Expression Gene Expression Profile Gene Mutation Gene Targeting Genes Genetic Genetic Polymorphism Goals Harvest Health Health Priorities Homeostasis Human In Vitro Knowledge Lead Medical Menopausal Status Messenger RNA Metabolic Bone Diseases Mission Modeling Molecular Mutagenesis Mutation Nature Osteoclasts Osteopenia Osteoporosis Osteoporosis prevention Pharmaceutical Preparations Pharmacotherapy Phenotype Physical activity Population Predisposition Prevention Proteins Public Health Quality of life Research Risk Series Siblings Skeletal Development Staging Time Tissue Differentiation Tissue Engineering Tissues Variant Woman Zebrafish aged base bone loss cost drug discovery effective therapy gene function genome wide association study human disease improved in vivo innovation men mutant new therapeutic target next generation sequencing novel osteoporosis with pathological fracture prevent public health relevance repaired screening sex skeletal skeletal disorder small molecule spine bone structure success tool

项目摘要

DESCRIPTION (provided by applicant): Bone fractures due to osteoporosis present a significant public health burden, high medical costs, and reduced quality of life in an increasingl aged population. It is estimated that 40-90% of variation in BMD may be due to genetic variability. Although more than 40 candidate genes for predisposition to osteoporosis have been identified, they represent less than 1% of the genetic variance of BMD at the population level, due to the large number of genes functioning in bone development and homeostasis. These studies identify osteoporosis as a major health problem, and emphasize the need for further research and better animal models to elucidate genetic factors underlying this disease. In the proposed studies, we will define the molecular and developmental nature of the newly identified zebrafish osteopenia mutant, droog(dro)tft92N, as a novel animal model for human osteoporosis. This research is significant and innovative in that it may implicate a new gene in the prevention of osteoporosis. In addition, these studies will validate the zebrafish mutant dro as a new model to improve our understanding of the genetic contributions leading to human osteoporosis, and as an in vivo screening tool to identify new therapeutic targets to treat human osteoporosis. Our proposed studies to establish a three dimensional (3D) in vitro cell culture model to study normal and dro mutant harvested cells will provide an innovative platform for small molecular screens to identify novel therapies for improved and effective treatment of human osteoporosis.

描述（由申请人提供）：由于骨质疏松症引起的骨折表现出巨大的公共卫生负担，高昂的医疗费用以及越来越大的人口的生活质量。据估计，BMD变异的40-90％可能是由于遗传变异性。尽管已经确定了40多个用于骨质疏松症的候选基因，但由于在骨发育和稳态中起作用大量基因，它们在人群水平上不到BMD遗传方差的1％。这些研究认为骨质疏松症是一个主要的健康问题，并强调需要进一步研究，并更好地阐明动物模型以阐明这种疾病的遗传因素。在拟议的研究中，我们将定义新鉴定的斑马鱼骨质减少突变体Droog（DRO）TFT92N的分子和发育性质，作为人类骨质疏松症的新型动物模型。这项研究具有重要意义和创新性，因为它可能暗示了一种新基因的预防骨质疏松症。此外，这些研究将验证斑马鱼突变体DRO，作为一种新的模型，以提高我们对导致人骨质疏松症的遗传贡献的理解，并成为一种体内筛查工具，以识别治疗人骨质疏松症的新治疗靶标。我们提出的研究建立了三维（3D）体外细胞培养模型，以研究正常和DRO突变的收获细胞，将为小分子筛选提供一个创新的平台，以鉴定新的疗法，以改善人类骨质疏松症。