Kidney molecular atlas project

描述（由申请人提供）： 肾脏疾病是主要的卫生保健费用之一。尽管肾脏对维持个体的正常生理平衡至关重要，但对创造功能器官的发育程序的理解相对较差。我们的目标是产生一个详细的空间地图的细胞表达的选定的调控基因在哺乳动物（小鼠）肾脏发育，以产生一个“分子解剖学”的发展肾脏。我们还将创造一系列转基因小鼠品系，以便对关键细胞类型进行快速鉴定和遗传操作。目标1：我们将进行一个全基因组的分析，在胚胎泌尿生殖系统的所有基因编码小鼠转录调节因子，配体和同源表面受体的表达。目标二：我们将产生一个高分辨率的部分原位杂交（SISH）地图的所有基因的表达在目的1在胎儿和新生儿的肾脏。目标3：我们将对肾小管缺陷小鼠肾脏和显微解剖的肾小管进行转录阵列分析，以识别并随后绘制肾小管特异性基因的表达。目标4：我们将使用BAC介导的转基因技术在特定的细胞群中表达荧光报告蛋白和Cre重组酶，用于细胞标记、细胞命运和遗传操作研究。

DESCRIPTION (provided by applicant): Kidney disease is one of the leading health-care costs. Despite the vital importance of the kidney to maintaining the normal physiological equilibrium of an individual, there is a relatively poor understanding of the developmental program that creates the functional organ. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian (mouse) kidney development to generate a "molecular anatomy" of the developing kidney. We will also create a series of transgenic mouse strains that will allow the ready identification and genetic manipulation of key cell types. Aim 1: We will perform a genome-wide analysis of the expression of all genes encoding mouse transcriptional regulators, ligands and cognate surface receptors in the embryonic urogenital system. Aim 2: We will generate a high resolution section in situ hybridization (SISH) map of the expression of all genes in Aim 1 in the fetal and neonatal kidney. Aim 3: We will perform transcriptional array analysis of renal tubule deficient mouse kidneys and micro-dissected kidney tubules to identify, and subsequently map the expression of tubule specific genes. Aim 4: We will use BAC-mediated transgenics to express fluorescent reporter proteins and Cre recombinase in specific cell populations for cell marking, cell fate and genetic manipulation studies.