Cyst induction and growth in ADPKD

ADPKD 中囊肿的诱导和生长

基本信息

批准号：
10474671
负责人：
Cristina Cebrian Ligero
金额：
$ 10万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2023-09-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10474671
关键词：
Ablation Address Affect Age Alleles Antibodies Automobile Driving Autosomal Dominant Polycystic Kidney Behavior Budgets Cell Aging Cell Death Cell Proliferation Cells Clonal Expansion Clone Cells Cues Cultured Cells Cyst Cystic Kidney Diseases Cystic kidney Data Daughter Development Disadvantaged Disease Disease Progression Distal Drug Combinations Embryo Epithelial cyst FDA approved Gene Expression Profile Generations Genetic Recombination Goals Growth Growth and Development function Henle&apos s loop Human Hypertension Image Incidence Individual Inflammation Inherited Injury Kidney Kidney Failure Label Lead Live Birth Loss of Heterozygosity Manuscripts Modeling Molecular Mus Mutant Strains Mice Mutate Mutation Nature Obstruction Outcome PKD1 gene Pain Pathologic Pathway interactions Patients Published Comment Renal function Role Severities Signal Transduction Somatic Mutation Source Stains Testing Therapeutic Time Tissues Tubular formation base cell motility cell type experimental study in vivo kidney cell mouse genetics mouse model mutant nephrogenesis novel strategies postnatal prevent

项目摘要

The requested budget will be used to generate data to finalize our manuscripts, to propose a mechanistic aim 1 and to address additional comments from the reviewers. Specifically, the following preliminary experiments will be covered by this R56: 1) Generation and characterization of high-recombination MADM models using Hprt-cre and UBC-cre mice, 2) Characterization of the Six2-cre and Ksp-cre MADM model, including staining with antibodies for proximal, Loop of Henle, distal and collecting tubule markers to characterize the tubular identify of the cysts, quantification of cyst number and size, and proliferation/senescence of cells in the cysts over time; and 3) We will perform live-imaging of mutant and control cells on developing kidneys induced with TAT-cre and characterize proliferation and cell migration of mutant cells at the inception of cyst development.

所请求的预算将用于生成数据以最终确定我们的手稿，提出机械目标 1 并解决审稿人的其他意见。具体来说，该 R56 将涵盖以下初步实验：1) 使用 Hprt-cre 和 UBC-cre 小鼠生成高重组 MADM 模型并对其进行表征，2) Six2-cre 和 Ksp-cre MADM 模型的表征，包括使用近端、亨利环、远端和集合管标记物的抗体进行染色，以表征肾小管识别囊肿，量化囊肿数量和大小，以及囊肿中细胞随时间的增殖/衰老； 3) 我们将对 TAT-cre 诱导的发育中的肾脏中的突变细胞和对照细胞进行实时成像，并在囊肿发育开始时表征突变细胞的增殖和细胞迁移。