A Database of Mammalian Neuronal Cell Types

描述(申请人提供)：神经细胞类型是大脑功能的基石，细胞类型之间的差异对于了解神经系统疾病至关重要。新的遗传和基因组资源越来越多地可用于识别和操纵小鼠的特定细胞类型。我们将创建一个通往这些试剂的统一门户，并建立一个与这些试剂整合和共享数据的平台，以促进在识别哺乳动物大脑神经细胞类型这一难题上取得进展。我们将实现一个可搜索的、免费共享的资源和实验结果开源数据库。我们将通过将单个切片与Allen Brain Reference Atlas进行比对来注释目标细胞类型在大约90个现有驱动/报告菌株中的解剖位置，并将在小鼠中使用新的慢病毒增强子陷阱策略开发新的菌株。对于细胞类型的一个子集，我们将进行基因组-基因表达谱分析，以增强对神经细胞类型之间关系的这种无偏见的度量的洞察力。我们将把细胞类型数据库和改进的图谱查看器与查看特定细胞类型的形态、生理和基因表达数据的工具相结合，并将这些数据与其他可用的脑图谱和基因组数据库联系起来。自由搜索和比较细胞类型特定表型和基因表达数据的能力将使科学界成员能够就特定细胞表型的分子基础提出具体假设，并改进神经元细胞类型的分类方案。 与公共健康相关：神经细胞类型是大脑的功能构件。我们将创建一个哺乳动物神经细胞类型的数据库。为了提高这一努力的有效性，我们将产生新的小鼠品系，允许特定细胞类型的基因靶向，并将描述使细胞类型彼此不同的基因表达模式。绝大多数脑部疾病是主要影响特定细胞类型的疾病，因此整合和提高我们对哺乳动物大脑中细胞类型的理解可能有助于对这些疾病的研究。

DESCRIPTION (provided by applicant): Neuronal cell types are the building blocks of brain function and differences between cell types are critical to understanding nervous system disease. New genetic and genomic resources are increasingly available for identifying and manipulating specific cell types in the mouse. We will create a unified gateway to these reagents and a platform for integrating and sharing data obtained with them to enhance progress on the difficult problem of identifying the neuronal cell types of the mammalian brain. We will implement a searchable, freely shared open source database of resources and experimental results. We will annotate the anatomical location of targeted cell types within each of ~90 existing driver/reporter strains by aligning individual sections to the Allen Brain Referenc Atlas and will develop new strains using a novel lentiviral enhancer trap strategy in mice. For a subset of cell types we will perform genome-gene expression profiling to enhance insights from this unbiased metric of relationships between neuronal cell types. We will integrate the cell type database and improved atlas viewer with tools for viewing cell type-specific morphology, physiology and gene expression data, and will link these data with other available brain atlas and genomic databases. The ability to freely search and compare cell-type specific phenotypes and gene expression data will enable members of the scientific community to develop specific hypotheses about the molecular bases of specific cellular phenotypes and to improve schemes for classifying neuronal cell types. PUBLIC HEALTH RELEVANCE: Neuronal cell types are the functional building blocks of the brain. We will create a Database of Mammalian Neuronal Cell-types. To enhance the usefulness of this effort we will generate new strains of mice that allow genetic targeting of specific cell types and will profile the gene expression patterns that make cell types different from one another. The great majority of brain diseases are diseases that primarily affect specific cell types, and therefore integrating and improving our understanding of cell types in the mammalian brain may help study of these diseases.