Technology Project: Genetic Tools and Resources for Orofacial Clefting Research

描述(申请人提供)：口腔裂伤是人类最常见的出生缺陷之一，大约每700名活产儿中就有1人受到影响。这一频率突显了颅面形态发生的复杂性，这需要对基因表达变化、细胞生理变化和形态发生运动进行精确调控。老鼠在促进我们对控制面部中部和上颚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开发新的小鼠遗传工具和提供对唇裂研究界至关重要的小鼠品系库来促进口面部裂伤研究。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被专门设计来支持口面部劈裂研究，由Face Base联盟的成员提供意见。这些品系将在我们为评估和质量控制表达Cre的小鼠品系而建立的流水线中进行表征。其次，我们将为进口、冷冻保存、遗传质量控制以及新的和现有的小鼠模型和工具品系的分布提供一个储存库，这些模型和工具品系对口腔裂隙研究非常重要。这些菌株将包括基因工程、自发发生和ENU诱导的模型。将积极向脸部基础联盟的成员和整个科学界征集新的口腔面部劈裂模型。我们将为杰克逊脸库创建一个公共网站，以促进这一资源的使用，并促进获取用于口腔面部研究的老鼠模型和工具。这些项目将共同为脸部基地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鼠标库服务，以加强口面部裂隙的研究。 与公共卫生相关：口腔裂伤是人类最常见的先天缺陷之一；其原因既有遗传因素，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，在人类群体中发现疾病的遗传原因是困难的。因此，具有明确的遗传背景和受控环境的遗传工具和动物模型对于理解面中部和腭部发育的遗传调控是重要的。

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.