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Core B

核心B

基本信息

批准号：
8744397
负责人：
DAN THEODORESCU
金额：
$ 23.47万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-23 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8744397
关键词：
AKT1 gene Address Alleles Animal Model Animals Breeding Cause of Death Cell Line Complex Data Diagnostic radiologic examination Ensure Future Generations Genes Genetic Genetic Models Genetically Engineered Mouse Genotype Goals Human Image Image Analysis Imaging Techniques Inbreeding Individual Knockout Mice Malignant Neoplasms Malignant neoplasm of prostate Metastatic Neoplasm to the Bone Modeling Mus Mutant Strains Mice Mutate Mutation Neck Neoplasm Metastasis PTEN gene Phenotype Prostate Prostatic Neoplasms Protocols documentation Reagent Research Personnel Resources Role Scheme Series Services Signal Pathway Signal Transduction Technical Expertise Testing Time Training Training Programs Training Support Transgenes Transgenic Animals Transgenic Organisms Tumor Suppressor Proteins Xenograft Model Xenograft procedure cost embryonic stem cell in vivo in vivo imaging member men mouse model novel null mutation programs prostate cancer model prostate carcinogenesis research study tumor tumor progression tumor xenograft tumorigenesis

项目摘要

The Core will perform two major functions: We will assist with the generation and analysis of xenograft tumor models, and generate novel genetically engineered mouse models for prostate tumorigenesis. The generation and analysis of xenografts tumor models is time consuming and requires specific technical expertise. We will provide technical assistance and training to facilitate the use of xenograft models. A major bottle-neck in the testing and generation of better mouse models of prostate cancer is combining standard genetic models with specific additional mutations. We will generate experimental animals in the Core, thereby removing much ofthe initial burden of complex transgenic experiments from the individual Projects within this Program. This will facilitate the use of such genetic models, and will minimize cost and delays due to lack of access to genetic models and lack of resources. Specifically, in support of the Aims of the three Projects within the Program we will: 1) Provide technical support and training for in vivo xenograft experiments and tumor imaging. Members ofthe Core will be involved in the planning and initiation of xenograft experiments, and will assist with in vivo imaging, induding Xenogen imaging and X-ray imaging of metastases to bone. 2) Generate novel combinations of genetic alterations in mice to address roles in prostate tumorigenesis. We will combine novel conditional mutations in Rala and Ralb with prostate specific deletion of the Pten tumor suppressor. Additionally, we will analyze a series of prostate specific PKN1 transgenes, and combine the most informative with a transgene in which constitutively active AKT1 is expressed in the prostate. 3) Generate mice with a targeted Pkn1 conditional null allele. Mice will be generated from ES cells with a targeted conditional mutation in the Pkn1 gene, and prostate-specific deletion of Pkn1 will be combined with the Pten null mutation, 4) Transfer transgenic prostate tumor models to a pure FVB strain background. All mutations will be transferred to a pure FVB strain background to simplify the analysis of prostate specific tumor phenotypes. By providing these services, we will allow the Program to begin to analyze prostate cancer progression more effectively using animal models.

核心将执行两个主要功能：我们将协助异种移植肿瘤模型的生成和分析，并生成用于前列腺肿瘤发生的新型基因工程小鼠模型。异种移植肿瘤模型的生成和分析是耗时的，并且需要特定的技术专长。我们将提供技术援助和培训，以促进异种移植模型的使用。测试和产生更好的前列腺癌小鼠模型的主要瓶颈是将标准遗传模型与特定的额外突变相结合。我们将在核心区培育实验动物，从而消除本计划中各个项目复杂转基因实验的最初负担。这将有助于使用这种遗传模型，并将最大限度地减少由于无法获得遗传模型和缺乏资源而造成的费用和延误。具体而言，为了支持该计划中三个项目的目标，我们将：1）为体内异种移植实验和肿瘤成像提供技术支持和培训。核心成员将参与异种移植实验的计划和启动，并将协助体内成像，包括Xenogen成像和骨转移的X射线成像。2)在小鼠中产生新的遗传改变组合，以解决前列腺肿瘤发生中的作用。我们将结合联合收割机新的条件突变在Rala和Ralb与前列腺特异性删除的Pten肿瘤抑制。此外，我们将分析一系列前列腺特异性PKN1转基因，并将最具信息性的转基因与组成型活性AKT1在前列腺中表达的转基因联合收割机结合。3)产生具有靶向Pkn1条件无效等位基因的小鼠。小鼠将由在Pknl基因中具有靶向条件突变的ES细胞产生，并且Pknl的前列腺特异性缺失将与Pten无效突变组合。4）将转基因前列腺肿瘤模型转移至纯FVB株背景。将所有突变转移至纯FVB菌株背景，以简化前列腺特异性肿瘤表型的分析。通过提供这些服务，我们将使该计划开始使用动物模型更有效地分析前列腺癌进展。