Food intake and obesity in cloned mice

克隆小鼠的食物摄入和肥胖

• 批准号: 7037784
• 负责人: Randall R. Sakai
• 金额: $ 39.46万
• 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 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037784
• 关键词: assistive reproductive technique; behavior test; behavioral /social science research tag; bioenergetics; biological models; body weight; disease /disorder etiology; embryo /fetus culture; epigenetics; gene environment interaction; genetically modified animals; glucose tolerance test; hormone regulation /control mechanism; in situ hybridization; laboratory mouse; longitudinal animal study; neuroendocrine system; nuclear transfer; obesity; overeating; phenotype; therapy adverse effect; weight gain

DESCRIPTION (provided by applicant): 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

描述（由申请人提供）：通过体细胞的核转移来克隆动物是一个科学重要的话题，也是政治上充电的。因此，严格的实验必须告知科学家和公众，并以最高的护理，控制和理解标准进行工作。该建议的目的是使用鼠标模型研究克隆过程的不良副作用。我们发现，肥胖的表型是在连续几代克隆的小鼠中保持的。即源自克隆的克隆，但并未通过种系以自然衍生的后代，这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。提出的实验将开始探索克隆小鼠肥胖的可能机制。 具体目的是：1）确定克隆小鼠的肥胖是在产后早期发育期间的肥大或代谢率差异的结果。我们假设克隆的小鼠是倍率和/或相对于对照的早期发育早期的能量消耗和代谢率较低。 2）测试肥胖克隆捍卫其体重升高的假设与其他肥胖动物相比，并鉴定出在克隆中改变的能量稳态的神经内分泌控制系统的组成部分； 3）测试以下假设，即因体外胚胎产生和/或体外机械操纵而导致克隆的体重和肥胖症（以及较小程度的体外操纵对照小鼠）。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，我们将一组当局组成了克隆过程本身（Yanagimachi和Yamazaki），肥胖（Woods），以及评估必要的行为，生理，内分泌和神经生物学参数（Sakai）。夏威夷大学（UH）开创了核转移技术的研究人员将产生克隆的小鼠以及对照动物群体。辛辛那提大学（UC）的小组将进行行为，生理和神经化学研究，以表型克隆小鼠及其对照。拟议的研究将在克隆的小鼠中提供第一组纵向研究，以检查体细胞克隆的长期后果。此外，获得的行为，生理和神经化学数据将增强我们对肥胖机制的理解，这是全球严重而又增长的慢性公共卫生问题