Golgb1 in Craniofacial Development

Golgb1 在颅面发育中的作用

基本信息

批准号：
8785671
负责人：
Yu Lan
金额：
$ 11.7万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-12-13 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8785671
关键词：
5&apos Splice Site Accounting Affect Alleles Amino Acids Applications Grants Biochemical Biological Birth Cell Proliferation Cell physiology Cells Cellular biology Chromosomes Cleft Palate Congenital Abnormality Counseling Cre-LoxP Data Defect Development Developmental Process Disease Embryo Ensure Ethylnitrosourea Exons Extracellular Matrix Family Foundations Gene Silencing Gene Targeting Generations Genes Genetic Genetic Screening Glycosaminoglycans Golgi Apparatus Golgi Targeting Grant Health Heart Hereditary Disease Human Individual Induced Mutation Integral Membrane Protein International Introns Investigation Knock-out Knockout Mice Knowledge LacZ Genes Lead Live Birth Mediating Membrane Mesenchyme Messenger RNA Molecular Mus Mutagenesis Mutant Strains Mice Mutation Neural Crest Cell Nucleotides Operative Surgical Procedures Organogenesis Palate Pathogenesis Pathology Pathway interactions Pattern Phenotype Play Prevention strategy Process Protein Glycosylation Protein Truncation Proteins Regulation Reporter Research Research Project Grants Reverse Transcriptase Polymerase Chain Reaction Role Sequence Analysis Site Solid Specificity Structure Terminator Codon Testing Tissues Vesicle Vesicle Transport Pathway base cell motility craniofacial craniofacial development developmental disease embryonic stem cell exome sequencing improved insight loss of function loss of function mutation molecular marker mutant novel palatal shelves palatogenesis premature promoter research study secretion process skeletal stem tissue culture trafficking transmission process

项目摘要

DESCRIPTION (provided by applicant): Cleft palate is a common major birth defect that requires surgical intervention shortly after birth and has significant long-term health implication for the affected individuals. Although there has been tremendous progress in the understanding of molecular regulation of palate development in the last twenty years, currently known genetic causes account for less than 20% of cleft palate pathology in humans. Through a phenotype-driven mutagenesis screen and whole exome sequencing analyses, we have identified a loss-of-function mutation in the Golgb1 gene in a new cleft palate mutant mouse strain. Golgb1 encodes a large transmembrane protein localized to the Golgi apparatus. Although several human developmental disorders have been associated with mutations in Golgi-associated proteins, few studies have characterized the roles of Golgi and Golgi-associated proteins in development and organogenesis. In this project, we will generate mice carrying an independent gene-targeted mutation in Golgb1 to confirm that loss of function of Golgb1 causes cleft palate. We will identify specific cellular, molecular, and morphogenetic processes during palate development that depend on Golgb1 function. These studies will provide novel insights into the molecular and cellular mechanisms of palate development and pathogenic mechanisms of craniofacial birth defects.

描述（由申请人提供）：left裂是一种常见的主要先天缺陷，需要在出生后不久进行手术干预，并且对受影响的个体具有显着的长期健康影响。尽管过去二十年来对味蕾发育的分子调节的理解取得了巨大进展，但目前已知的遗传原因占人类裂口病理学的20％。通过表型驱动的诱变筛选和整个外显子组测序分析，我们已经确定了新的left裂突变小鼠菌株中GolGB1基因的功能丧失突变。 Golgb1编码局部固定在高尔基体设备的大型跨膜蛋白。尽管几种人类发育障碍与高尔基相关蛋白的突变有关，但很少有研究表征高尔基体和高尔基体相关蛋白在发育和器官发生中的作用。在这个项目中，我们将生成在Golgb1中携带独立基因靶向突变的小鼠，以确认Golgb1功能的损失会导致left裂。我们将在依赖GolGB1功能的口服发育过程中确定特定的细胞，分子和形态发生过程。这些研究将提供有关颅面先天缺陷的口服发育和致病机制的分子和细胞机制的新见解。