Technology Project: Genetic Tools and Resources for Orofacial Clefting Research

描述（由申请人提供）：口面裂是人类最常见的出生缺陷之一，影响大约1/700的活产婴儿。这种频率突出了颅面形态发生的复杂性，这需要精确调节基因表达变化，细胞生理学和形态发生运动的改变。老鼠在推进我们对控制中面部和上腭发育的机制的理解方面发挥了重要作用。然而，未来的进展将需要一套日益复杂的遗传模型和工具。该项目的总体目标是通过产生新的小鼠遗传工具和提供对裂研究社区至关重要的小鼠品系库来促进口面裂研究。首先，我们将产生诱导型和组成型Cre重组酶驱动系作为新的遗传工具。这些新的小鼠品系将专门设计用于支持口面裂研究，并由Face Base财团成员提供投入。这些品系将在我们建立的用于Cre表达小鼠品系的评价和质量控制的管道中进行表征。第二，我们将提供一个进口，冷冻保存，遗传质量控制，和分配的新的和现有的小鼠模型和工具株重要的口面裂研究的知识库。这些菌株将包括基因工程、自发发生和ENU诱导的模型。新的模型口面裂将积极征求成员的脸基地财团和科学界在广大。我们将为杰克逊面部基础知识库创建一个公共网站，以促进对该资源的使用，并方便访问鼠标模型和口面研究工具。这些项目将为Face Base成员和一般科学界提供新的研究工具，新颖的遗传模型和全面的小鼠库服务，以加强口面裂的研究。 公共卫生相关性：口面裂是人类最常见的出生缺陷之一;原因既有遗传因素，也有环境因素。由于人类的极端异质性以及环境和营养变量的多样性，在人群中发现疾病的遗传原因是困难的。因此，具有明确遗传背景和受控环境的遗传工具和动物模型对于了解中面部和腭发育的遗传调控非常重要。

DESCRIPTION (provided by applicant): Orofacial clefting is one of the most common birth defects in humans, affecting approximately 1 in 700 live births. This frequency highlights the complexity of craniofacial morphogenesis, which requires precise regulation of gene expression changes, alterations in cell physiology and morphogenic movements. The mouse has played an instrumental role in advancing our understanding of the mechanisms that govern mid- face and palate development. Future progress, however, will require an increasingly sophisticated set of genetic models and tools. The overall goal of this project is to facilitate orofacial clefting research by generating new mouse genetic tools and by providing a repository of mouse strains critical for clefting research community. First, we will generate both inducible and constitutive Cre recombinase driver lines as new genetic tools. These new mouse strains will be designed specifically to support orofacial clefting research, with input from members of the Face Base consortium. These lines will be characterized in our established pipeline for evaluation and quality control of Cre-expressing mouse strains. Second, we will provide a repository for importation, cryopreservation, genetic quality control, and distribution of new and existing mouse models and tool strains important for orofacial clefting research. Such strains will include genetically engineered, spontaneously occurring, and ENU-induced models. New models for orofacial clefting will be actively solicited from members of the Face Base consortium and from the scientific community at large. We will create a public website for the Jackson Face Base Repository to promote the use of this resource and to facilitate access to mouse models and tools for orofacial research. Together, these projects will provide both Face Base members and the general scientific community with new research tools, novel genetic models, and comprehensive mouse repository services to enhance research in orofacial clefting. PUBLIC HEALTH RELEVANCE: Orofacial clefting is one of the most common birth defects in humans; causes are both genetic and environmental. Discovery of the genetic cause of disease in human populations is difficult due to extreme heterogeneity in humans and to the diversity of environmental and nutritional variables. Consequently, genetic tools and animal models with defined genetic backgrounds and controlled environments are important for understanding genetic regulation of mid-face and palate development.