Validation of a Novel Genetic Model for Neural Regeneration

神经再生新遗传模型的验证

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7938603
• 关键词: Adult; Amaze; Ambystoma; Animal Model; Brain; Cell Line; Communities; Engineering; Exhibits; Genes; Genetic; Genetic Models; Genomics; Goals; Grant; Human; Journals; Mammals; Maps; Mexican; Modeling; Mus; Natural regeneration; Nerve Regeneration; Organism; Orthologous Gene; Pathway interactions; Patients; Regenerative Medicine; Research Infrastructure; Salamander; Science; Scientist; Series; Spinal Cord; Transgenic Organisms; Validation; Vertebrates; comparative genomics; gene function; human disease; in vivo; member; mouse model; nerve stem cell; nestin protein; novel; organ regeneration; regenerative; relating to nervous system; response; tool

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视为科学中25个未解决的问题之一。 400多年来，科学家一直在研究Axolotl或墨西哥sal的惊人再生能力。这些惊人的生物可以以几乎完美的忠诚来再生其身体的大部分部位。但是，近年来，Axolotl缺乏成为“ Omics”时代理想模型生物所需的严格遗传工具。该GO应用程序的成员开创了为Axolotl创建遗传工具的最新进展。现在，我们可以使用我们的新工具来创建Axolotl直系同源基因阵列，以匹配小鼠和人类可用的阵列。此外，我们可以设计转基因轴突以定义体内基因功能。我们的Go Grant的目的是验证Axolotl作为理想的遗传生物，以将完全再生脊椎动物（Axolotl）与哺乳动物进行比较。当前的遗传模型作为成年人表现出明显的再生能力。再生医学的目的是增强患者的自然再生能力。对于映射神经再生的相关遗传途径，不存在更强的工具，而不是经过验证的Axolotl模型。在此GO提案的两年中，我们将直接建模许多鼠模型，用于轴突中大脑和脊髓的神经再生，创建靶向神经特异性的Axolotl基因阵列，并将Axolotl对小鼠的遗传反应进行对比，以定义再生的途径。我们已经产生了正在经历初始表征的Axolotl神经干细胞系（GFP+） - 将在此建议中与小鼠NSC进行比较。我们还将创建一系列转基因Axolotl模型，以匹配当前现有的鼠标模型，例如GFAP：GFP和NESTIN：GFP。所有这些可交付成果都将向科学界充分使用。这个宏伟的机会建议的目的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，以将Axolotl的惊人再生能力与已建立的人类疾病模型进行比较。利用比较基因组学将允许鉴定脊椎动物再生所需的途径。