Food intake and obesity in cloned mice

通过体细胞核移植克隆动物是一个重要的科学课题，也是一个政治问题。 充电。因此，严格的实验必须让科学家和公众了解， 大，并以最高标准的照顾，控制和理解进行工作。的 这项建议的目的是调查克隆过程中的一个不良副作用，肥胖，使用 小鼠模型我们已经发现肥胖表型在连续几代中保持不变， 克隆小鼠;即克隆来源于克隆，但它不是通过生殖系自然衍生的 这表明克隆小鼠的肥胖表型是一种表观遗传，而不是遗传 现象拟议中的实验将开始探索克隆人肥胖的可能机制。 小鼠 具体的目的是：1）确定克隆小鼠肥胖是否是过度进食的结果， 出生后早期发育过程中代谢率的差异。我们假设克隆小鼠 在发育早期具有较低的能量消耗和代谢率 2）为了验证肥胖克隆体与其他克隆体相比， 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， 在克隆中发生了改变; 3）为了验证克隆中体重增加和肥胖的假设（以及 体外操作的对照小鼠在较小程度上）由体外胚胎产生和/或体外 机械操作总的来说，这些实验将提供有关克隆的详细信息， 以及用于产生克隆的过程的长期影响。 为了实现这一目标，我们已经组建了一个克隆过程本身的权威团队（柳町 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）的研究人员率先提出了 核移植技术将产生克隆小鼠以及对照动物组。本集团于 辛辛那提大学（UC）将进行行为、生理和神经化学研究， 表型的克隆小鼠和他们的控制。这项研究将提供第一套纵向 在克隆小鼠中进行的研究，检查体细胞克隆的长期后果。此外该 获得的行为、生理和神经化学数据将增强我们对 肥胖症是一个严重且日益严重的全球慢性公共卫生问题。

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.