Food intake and obesity in cloned mice

克隆小鼠的食物摄入和肥胖

• 批准号: 7766981
• 负责人: Randall R. Sakai
• 金额: $ 35.96万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7766981
• 关键词: Adult; Adult Children; Adverse effects; Animal Model; Animals; Behavioral; Body Weight; Body fat; Caring; Cells; Charge; Chronic; Cloning; Conflict (Psychology); Consumption; Control Animal; Control Groups; Data; Development; Eating; Embryo; Endocrine; Energy Metabolism; Epigenetic Process; Etiology; Generations; Genetic Phenomena; Germ Lines; Goals; Hawaii; Homeostasis; Human; Hyperphagia; In Vitro; Laboratories; Livestock; Long-Term Effects; Longevity; Longitudinal Studies; Mammals; Mechanics; Metabolic; Monitor; Mus; Neurobiology; Neurosecretory Systems; Obesity; Organ; Phenotype; Physiological; Process; Production; Public Health; Relative (related person); Reporting; Research; Research Personnel; Scientist; Somatic Cell; System; Techniques; Technology; Testing; Tissues; Transplantation; Universities; Weight Gain; Wood material; Work; animal cloning; authority; high standard; mouse model; neurochemistry; nuclear transfer; offspring; postnatal; research study; somatic cell nuclear transfer

Cloning animals by nuclear transfer of somatic cells is a scientifically important topic that is also politically charged. It is therefore imperative for rigorous experimentation to inform both the scientist and the public at large, and that the work be conducted with the highest standards of care, control and understanding. The goal of this proposal is to investigate an undesirable side effect of the cloning process, obesity, using a mouse model. We have found that the obese phenotype is maintained over successive generations of cloned mice; i.e. clones derived from clones, but it is not passed through the germ line to naturally derived offspring, suggesting that the obese phenotype of cloned mice is an epigenetic rather than a genetic phenomenon. Proposed experiments will begin to explore possible mechanisms for the obesity in cloned mice. Specific Aims are: 1) To determine whether obesity in cloned mice is the result of hyperphagia or differences in metabolic rate during early postnatal development. We hypothesize that cloned mice are hyperphagic and/or have lower energy expenditure and metabolic rate early in development relative to controls; 2) To test the hypothesis that obese clones defend their elevated body weight comparably to other obese animals, and to identify components of the neuroendocrine control system of energy homeostasis that are altered in clones; and 3) To test the hypothesis that increased body weight and obesity in cloned (and in vitro-manipulated control mice to a lesser extent) result from in vitro embryo production and/or in vitro mechanical manipulation. Collectively, these experiments will provide detailed information about clones as well as the long-term effects of the process used to generate the clones. To accomplish this, we have put together a team of authorities on the cloning process itself (Yanagimachi and Yamazaki), on obesity (Woods), and on assessment of the requisite behavioral, physiological, endocrine and neurobiological parameters (Sakai). Investigators at the University of Hawaii (UH) who pioneered the nuclear transfer technique will generate the cloned mice as well as the control animal groups. The group at the University of Cincinnati (UC) will conduct behavioral, physiological and neurochemical studies to phenotype the cloned mice and their controls. The proposed research will provide the first set of longitudinal studies in cloned mice that examine the long-term consequences of somatic cell cloning. In addition, the behavioral, physiological, and neurochemical data obtained will enhance our understanding of the mechanisms of obesity, a serious and growing chronic public health issue worldwide.

通过核细胞的核转移克隆动物是一个科学重要的话题，也是政治上的 带电。因此，严格的实验必须告知科学家和公众 很大，并且以最高的护理，控制和理解标准进行工作。这 该建议的目标是研究克隆过程的不良副作用，肥胖，使用 鼠标模型。我们发现，肥胖表型是在连续几代人的 克隆小鼠；即来自克隆的克隆 后代，表明克隆小鼠的肥胖表型是一种表观遗传学，而不是遗传 现象。建议的实验将开始探索克隆肥胖的可能机制 老鼠。 具体目的是：1）确定克隆小鼠的肥胖是应激症还是 早期产后发展期间代谢率的差异。我们假设克隆小鼠是 相比 控件； 2）检验肥胖克隆捍卫其体重升高的假设与其他 肥胖动物，并确定能量稳态的神经内分泌控制系统的组成部分 克隆改变； 3）检验以克隆增加体重和肥胖的假设（以及 体外胚胎产生和/或体外，体外操纵的对照小鼠的体外对照小鼠的较小程度） 机械操作。总的来说，这些实验将提供有关克隆的详细信息 以及用于生成克隆的过程的长期影响。 为了实现这一目标，我们将一个当局团队组成了克隆过程本身（Yanagimachi 和Yamazaki），关于肥胖（树林），并评估必要的行为，生理，内分泌 和神经生物学参数（Sakai）。夏威夷大学（UH）的调查人员开创了 核转移技术将产生克隆的小鼠以及对照动物组。小组在 辛辛那提大学（UC）将进行行为，生理和神经化学研究 克隆小鼠的表型及其对照。拟议的研究将提供第一组纵向 对克隆小鼠的研究，检查了体细胞克隆的长期后果。另外， 获得的行为，生理和神经化学数据将增强我们对 肥胖机制，全世界严重而越来越多的慢性公共卫生问题。