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重要的科学课题，也是一个充满政治色彩的课题。因此，严格的实验必须向科学家和广大公众提供信息，并以最高标准的谨慎、控制和理解进行工作。这项提案的目的是使用小鼠模型来研究克隆过程的不良副作用，肥胖症。我们已经发现，肥胖表型在连续几代克隆小鼠中得以维持;即，从克隆衍生的克隆，但它不会通过生殖系传递给自然衍生的后代，这表明克隆小鼠的肥胖表型是表观遗传而不是遗传现象。拟议中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出生后早期发育过程中摄食过多或代谢率差异的结果。我们假设克隆小鼠在发育的早期具有高摄食性和/或较低的能量消耗和代谢率; 2）验证肥胖克隆小鼠与其他肥胖动物相比体重增加的假说，并鉴定克隆小鼠中改变的能量稳态神经内分泌控制系统的组成部分;和3）检验克隆小鼠（以及较小程度上的体外操作对照小鼠）的体重增加和肥胖是由体外胚胎生产和/或体外机械操作引起的假设。总的来说，这些实验将提供有关克隆的详细信息，以及用于产生克隆的过程的长期影响。 为了实现这一目标，我们组建了一个克隆过程本身（柳町和山崎），肥胖（伍兹）和评估必要的行为，生理，内分泌和神经生物学参数（酒井）的权威团队。夏威夷大学（UH）的研究人员是核移植技术的先驱，他们将产生克隆小鼠和对照动物组。辛辛那提大学（UC）的研究小组将对克隆小鼠及其对照组进行行为、生理和神经化学研究。这项拟议中的研究将提供第一套克隆小鼠的纵向研究，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，肥胖是一个严重且日益严重的全球慢性公共卫生问题