Validation of a Novel Genetic Model for Neural Regeneration

神经再生新遗传模型的验证

基本信息

批准号：
7938603
负责人：
Edward W Scott
金额：
$ 102.42万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2013-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (Provided by Applicant): In 2005, Science magazine identified understanding organ regeneration as one of the top 25 unanswered questions in science. For over 400 years scientists have been studying the amazing regenerative capacity of the Axolotl or Mexican Salamander. These amazing creatures can regenerate most parts of their bodies with near perfect fidelity. However, in recent years the axolotl has lacked the rigorous genetic tools required to be an ideal model organism for the "Omics" era. Recent advances in creating the genetic tools for the Axolotl have been pioneered by members of this GO application. Using our novel tools we can now create axolotl ortholog gene arrays to match those available for mice and humans. In addition, we can engineer transgenic axolotls to define gene functions in vivo. The goal of our GO grant is to validate the axolotl as an ideal genetic organism to compare a fully regenerative vertebrate (axolotl) to mammals. No current genetic model exhibits significant regenerative capacity as an adult. The goal of Regenerative Medicine is to heighten a patient's natural regenerative capacities. No stronger tool will exist for mapping relevant genetic pathways for neural regeneration then a validated axolotl model. In the two years of this GO proposal we will directly model many of the murine models for neural regeneration of the brain and spinal cord in the axolotl, create targeted neural specific axolotl gene arrays, and contrast the genetic responses of the axolotl to the mouse in order to define the pathways of regeneration. We have already generated axolotl neural stem cell lines (Gfp+) that are undergoing initial characterization - they will be compared to mouse NSC in this proposal. We will also create a series of transgenic axolotl models to match currently existing mouse models such as GFAP:Gfp and Nestin:GFP. All of these deliverables will be made fully available to the scientific community. The goal of this Grand Opportunity proposal is to create novel research infrastructure for Regenerative Medicine. We will create the genomic tools necessary to compare the amazing regenerative capacity of the Axolotl to established mouse models of human disease. Utilizing comparative genomics will allow the identification of the pathways required for vertebrate animal regeneration as an adult.

描述（由申请人提供）： 2005 年，《科学》杂志将理解器官再生列为科学界 25 个尚未解答的首要问题之一。 400 多年来，科学家们一直在研究蝾螈或墨西哥蝾螈惊人的再生能力。这些神奇的生物可以以近乎完美的保真度再生身体的大部分部位。然而，近年来，蝾螈缺乏成为“组学”时代理想模式生物所需的严格遗传工具。该 GO 应用程序的成员在创建蝾螈遗传工具方面取得了最新进展。使用我们的新工具，我们现在可以创建蝾螈直向同源基因阵列，以匹配小鼠和人类可用的基因阵列。此外，我们可以改造转基因美西螈来定义体内基因功能。我们 GO 资助的目标是验证蝾螈作为一种理想的遗传生物，以将完全再生的脊椎动物（蝾螈）与哺乳动物进行比较。目前没有任何遗传模型表现出成年后显着的再生能力。再生医学的目标是提高患者的自然再生能力。没有比经过验证的蝾螈模型更强大的工具来绘制神经再生的相关遗传途径。在这个 GO 提案的两年内，我们将直接模拟许多用于蝾螈大脑和脊髓神经再生的小鼠模型，创建有针对性的神经特异性蝾螈基因阵列，并对比蝾螈与小鼠的遗传反应以确定再生途径。我们已经生成了蝾螈神经干细胞系 (Gfp+)，正在进行初步表征 - 在本提案中它们将与小鼠 NSC 进行比较。我们还将创建一系列转基因蝾螈模型，以匹配现有的小鼠模型，例如 GFAP:Gfp 和 Nestin:GFP。所有这些成果都将完全提供给科学界。这一重大机遇提案的目标是为再生医学创建新颖的研究基础设施。我们将创建必要的基因组工具，将蝾螈惊人的再生能力与已建立的人类疾病小鼠模型进行比较。利用比较基因组学将能够识别脊椎动物成年后再生所需的途径。