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（申请人提供）： 2005年，《科学》杂志将了解器官再生列为科学界25个未解之谜之一。400多年来，科学家们一直在研究美西蝾螈或墨西哥蝾螈惊人的再生能力。这些神奇的生物可以近乎完美地再生它们身体的大部分。然而，近年来，美西螈缺乏严格的遗传工具，无法成为“组学”时代的理想模式生物。最近在为蝾螈创造遗传工具方面的进展是由GO应用程序的成员开创的。使用我们的新工具，我们现在可以创建美西蝾螈直系同源基因阵列，以匹配小鼠和人类的基因阵列。此外，我们可以设计转基因蝾螈，以确定体内基因功能。我们的GO赠款的目标是验证美西螈作为一个理想的遗传生物体比较完全再生脊椎动物（美西螈）哺乳动物。目前没有任何遗传模型显示出成年后的显著再生能力。再生医学的目标是提高患者的自然再生能力。没有更强大的工具将存在映射相关的神经再生的遗传途径，然后验证蝾螈模型。在这两年的GO提案中，我们将直接模拟许多用于美西螈大脑和脊髓神经再生的小鼠模型，创建靶向神经特异性美西螈基因阵列，并将美西螈的遗传反应与小鼠进行对比，以确定再生途径。我们已经产生了蝾螈神经干细胞系（GFP+），正在进行初步表征-他们将在本提案中与小鼠NSC进行比较。我们还将创建一系列转基因蝾螈模型，以匹配目前现有的小鼠模型，如GFAP：GFP和Nestin：GFP。所有这些交付品都将向科学界充分提供。这个大机会提案的目标是为再生医学创造新的研究基础设施。我们将创建必要的基因组工具，以比较美西螈惊人的再生能力，以建立人类疾病的小鼠模型。利用比较基因组学将允许鉴定脊椎动物作为成年动物再生所需的途径。