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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.

所要求的预算将用于生成数据，以最终确定我们的手稿，提出一个机械目标1，并处理审查人员的其他意见。具体而言，该R56将涵盖以下初步实验：1）使用Hprt-cre和UBC-cre小鼠的高重组MADM模型的生成和表征，2）Six 2-cre和Ksp-cre MADM模型的表征，包括用近端、Henle环、远端和集合小管标记物的抗体染色以表征肾小管上皮细胞的表达。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;和3）我们将在用TAT-cre诱导的发育中的肾脏上进行突变和对照细胞的活体成像，并表征在囊肿发育开始时突变细胞的增殖和细胞迁移。