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）：通过体细胞核移植克隆动物是一个具有重要科学意义的话题，同时也具有政治色彩。因此，严格的实验必须告知科学家和广大公众，并且工作必须以最高标准的护理、控制和理解进行。该提案的目标是使用小鼠模型研究克隆过程中的不良副作用，即肥胖。我们发现，肥胖表型在连续几代的克隆小鼠中得以维持。即克隆衍生自克隆，但它不会通过种系传递给自然衍生的后代，这表明克隆小鼠的肥胖表型是一种表观遗传现象，而不是遗传现象。拟议的实验将开始探索克隆小鼠肥胖的可能机制。 具体目标是： 1) 确定克隆小鼠的肥胖是否是由于进食过多或出生后早期发育过程中代谢率差异造成的。我们假设克隆小鼠在发育早期相对于对照小鼠食量过多和/或具有较低的能量消耗和代谢率； 2) 检验肥胖克隆与其他肥胖动物相比能够维持较高体重的假设，并确定克隆中发生改变的能量稳态神经内分泌控制系统的组成部分； 3) 检验以下假设：克隆小鼠（以及较小程度的体外操作对照小鼠）体重增加和肥胖是由体外胚胎生产和/或体外机械操作造成的。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，我们组建了一个权威团队，负责克隆过程本身（柳町和山崎）、肥胖问题（伍兹）以及必要的行为、生理、内分泌和神经生物学参数评估（酒井）。率先采用核移植技术的夏威夷大学 (UH) 研究人员将培育出克隆小鼠以及对照动物组。辛辛那提大学 (UC) 的研究小组将进行行为、生理和神经化学研究，以对克隆小鼠及其对照进行表型分析。拟议的研究将提供第一组针对克隆小鼠的纵向研究，以检验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，肥胖是全球范围内严重且日益严重的慢性公共卫生问题