Technology Project: Genetic Tools and Resources for Orofacial Clefting Research

描述（由申请人提供）：口面部裂是人类最常见的出生缺陷之一，影响大约700个活产婴儿。这种频率突出颅面形态发生的复杂性，这需要精确调节基因表达变化，细胞生理和形态发生运动的改变。小鼠在促进我们对中脸和上颚发育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腭裂研究社区至关重要的小鼠品系库来促进口腔面部腭裂研究。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在Face Base联盟成员的投入下，专门设计用于支持口面部裂研究。这些品系将在我们建立的cre表达小鼠品系评估和质量控制管道中进行表征。其次，我们将为进口、冷冻保存、遗传质量控制和分发新的和现有的小鼠模型和工具菌株提供一个库，这些模型和工具菌株对口腔面部裂的研究很重要。这些菌株将包括基因工程的、自发发生的和enu诱导的模型。面部裂的新模型将从Face Base联盟的成员和整个科学界积极征求。我们将为Jackson Face Base Repository创建一个公共网站，以促进该资源的使用，并方便访问用于口腔面部研究的小鼠模型和工具。总之，这些项目将为Face Base成员和一般科学界提供新的研究工具、新的遗传模型和全面的小鼠库服务，以加强对口腔面部裂的研究。

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.