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(申请人提供)：通过体细胞核移植克隆动物是一个科学上重要的话题，也是一个充满政治色彩的话题。因此，严格的实验必须告知科学家和广大公众，并以最高标准的谨慎、控制和理解进行工作。这项提议的目的是使用小鼠模型来研究克隆过程中的一种不良副作用--肥胖。我们发现，肥胖表型在连续几代克隆小鼠中保持不变；即来自克隆的克隆，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一种表观遗传现象，而不是一种遗传现象。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由于过度吞噬还是出生后早期发育过程中代谢率的差异所致。我们假设克隆小鼠具有高吞噬能力和/或在发育早期比对照组有更低的能量消耗和代谢率；2)测试肥胖克隆比其他肥胖动物更好地保护它们超重的假设，并确定克隆小鼠能量稳态的神经内分泌控制系统的组件；以及3)测试克隆小鼠(和体外操纵的对照小鼠在较小程度上)的体重增加和肥胖是体外胚胎生产和/或体外机械操作导致的假说。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。 为了做到这一点，我们组建了一个权威团队，负责克隆过程本身(柳内町和山崎)、肥胖(伍兹)以及必要的行为、生理、内分泌和神经生物学参数的评估(Sakai)。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)的研究小组将进行行为、生理和神经化学研究，以确定克隆小鼠和它们的对照组的表型。这项拟议的研究将在克隆小鼠身上提供第一组纵向研究，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，肥胖是一个严重的、日益严重的全球慢性公共卫生问题。