Kidney molecular atlas project

描述(由申请人提供)： 肾脏疾病是主要的医疗费用之一。尽管肾脏对维持个体的正常生理平衡至关重要，但人们对创造功能器官的发育程序的了解相对较少。我们的目标是生成哺乳动物(小鼠)肾脏发育过程中选定调控基因的细胞表达的详细空间图，以生成发育中的肾脏的“分子解剖”。我们还将创造一系列转基因小鼠品系，使关键细胞类型的鉴定和遗传操作变得容易。目的1：我们将对所有编码小鼠转录调节因子、配体和同源表面受体的基因在胚胎泌尿生殖系统中的表达进行全基因组分析。目的2：建立胎儿和新生儿肾脏AIM 1基因表达的高分辨切片原位杂交图谱。目的：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，以鉴定并定位小管特异基因的表达。目的：我们将利用BAC介导的转基因技术在特定的细胞群体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的研究。

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.