Craniofacial Gene Discovery

颅面基因发现

• 批准号: 6641945
• 负责人: LEAH RAE B DONAHUE
• 金额: $ 40.75万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6641945
• 关键词: X ray; animal genetic material tag; biotechnology; blood chemistry; computed axial tomography; congenital oral /facial /cranial defect; craniofacial dysostosis; densitometry; disease /disorder model; electroretinography; gene expression; gene mutation; genetic disorder; genetic disorder diagnosis; genetic markers; genetic screening; genotype; laboratory mouse; linkage mapping; molecular cloning; northern blottings; photon absorptiometry; polymerase chain reaction; scanning electron microscopy; southern blotting

DESCRIPTION (provided by applicant): The objectives of the proposed research are to identify and characterize in mice craniofacial disorders that are reliable genetic and physiological models for human craniofacial dysmorphologies and to share these models with the scientific public. The proposed research will include screening for new spontaneous and induced mutations, comprehensive genetic studies, preliminary characterization studies (clinical examination, basic histology, evaluation of bone density and skeletal anomalies, dentition, vision and hearing), and identification of the mutated gene in the best models by candidate gene testing and positional cloning. We will provide these models to the scientific community expeditiously via website notification and will distribute live mice using programs already in place at The Jackson Laboratory. This proposal has three specific aims: 1. To discover and characterize (genetically and phenotypically) new mouse craniofacial mutations to provide the scientific community with model systems for research on facial, dental, eye, ear, and skull development and mouse models of human craniofacial syndromes. 2. To identify the mutated genes in three new mutants already genetically mapped and partially characterized: Dhe, a semi-dominant mutation causing an underdeveloped lower jaw, abnormal tooth development, small ears, and a sparse, rough coat; Lse, a semi-dominant mutation causing low set ears, skull and eye abnormalities, and nee, a recessive mutation causing a blunted face, bulging eyes, and intermediate hearing loss. 3. To execute a sharing plan whereby new models will be made available rapidly to the scientific community through our established web sites and live mice will be distributed via the existing shipping program within The Jackson Laboratory.

描述（由申请人提供）：拟议研究的目的是识别和表征小鼠颅面疾病，这些疾病是人类颅面畸形的可靠遗传和生理模型，并与科学公众分享这些模型。拟议的研究将包括筛选新的自发突变和诱导突变、综合遗传学研究、初步表征研究（临床检查、基础组织学、骨密度和骨骼异常评估、牙列、视力和听力）以及识别突变基因。通过候选基因测试和定位克隆建立最佳模型。我们将通过网站通知迅速向科学界提供这些模型，并将使用杰克逊实验室已有的程序分发活体小鼠。该提案有三个具体目标： 1. 发现并表征（遗传和表型）新的小鼠颅面突变，为科学界提供用于研究面部、牙齿、眼睛、耳朵和颅骨发育的模型系统以及人类颅面的小鼠模型综合症。 2. 鉴定已进行基因图谱和部分表征的三个新突变体中的突变基因：Dhe，一种半显性突变，导致下颌发育不全、牙齿发育异常、耳朵小以及毛发稀疏、粗糙； Lse 是一种半显性突变，导致耳朵位置低、头骨和眼睛异常；nee 是一种隐性突变，导致面部迟钝、眼睛凸出和中度听力损失。 3. 执行共享计划，通过我们已建立的网站向科学界快速提供新模型，并通过杰克逊实验室内现有的运输计划分发活体小鼠。