Food intake and obesity in cloned mice

通过体细胞核移植克隆动物是一个科学上的重要话题，也是一个政治上的话题 已被起诉。因此，严格的实验必须同时告知科学家和公众 这项工作应以最高标准的关怀、控制和理解进行。这个 这项提议的目标是调查克隆过程中的一个不良副作用，肥胖，使用 老鼠模型。我们发现，肥胖的表型在连续几代人中保持不变。 克隆鼠；即从克隆体衍生而来的克隆体，但不是通过生殖系自然派生的 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人肥胖的可能机制 老鼠。 具体目标是：1)确定克隆小鼠的肥胖是由于过度吞噬还是由于 出生后早期发育过程中代谢率的差异。我们假设克隆的小鼠是 高摄食性和/或发育早期的能量消耗和代谢率低于 对照；2)检验这样的假设：肥胖的克隆人与其他克隆人相比，可以更好地保护他们超重的体重 肥胖动物，并确定能量动态平衡的神经内分泌控制系统的组件 在克隆中改变；以及3)检验克隆(和克隆中)体重增加和肥胖的假设 体外操作的对照小鼠)来自体外胚胎生产和/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，如下所示 以及用于产生克隆的过程的长期影响。 为了做到这一点，我们组建了一个负责克隆过程本身的权威团队(柳马町 和山崎)，关于肥胖(伍兹)，以及对必要的行为、生理、内分泌的评估 和神经生物学参数(Sakai)。夏威夷大学(UH)的研究人员是这项研究的先驱 核移植技术将产生克隆小鼠和对照动物组。该小组位于 辛辛那提大学(UC)将进行行为、生理和神经化学研究 克隆小鼠及其对照小鼠的表型。拟议的研究将提供第一套纵向的 在克隆小鼠中研究体细胞克隆的长期后果。此外， 所获得的行为、生理和神经化学数据将增强我们对 肥胖是世界范围内一个严重且日益严重的慢性公共卫生问题。

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.