ALLOMETRIC GROWTH IN GIANT TRANSGENIC RODENTS

巨型转基因啮齿动物的异速生长

• 批准号: 3447443
• 负责人: BRIAN SHEA
• 金额: $ 5.32万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447443
• 关键词: aging; body weight; disease /disorder model; genetic manipulation; genetically modified animals; growth /development; hormone regulation /control mechanism; insulinlike factor; laboratory mouse; microscopy; model design /development; nucleic acid hybridization; postnatal growth disorder; skeletal system; somatotropin

The objective is to use transgenic mice (MTrGH-Palmiter et al., 1982) as an experimental model for the study of the effects of elevated levels of GH and IGF-I on organ and somatic growth. The specific problem to be analysed is whether the size and shape changes of the organs and musculoskeletal system in the giant transgenic mice results from general allometric effects (i.e. the extension of relative growth patterns of their normal-size littermate controls) or specific effects on particular target organ and regions. The hypothesis to be tested is that all changes in size and proportions of internal organs and the musculoskeletal system in the giant transgenic mice result from general size factors, or the differential extension of patterns of growth allometry characterizing the normal-sized controls. This hypothesis will be tested with methodological approaches drawn from studies of evolutionary morphology and not usually applied to normal and abnormal growth. These methodologies relate to ontogenetic allometry (relative growth), heterochrony (integration of size, shape, and timing parameters), and Wright's (1932) hierarchy of size factors or influences (general, group and special). This research is directly relevant to the hormonal control of organ and skeletal proportions during ontogeny in normal and abnormal growth. The transgenic mice provide an important model for the study of effects of prolonged exposure to abnormally high levels of growth hormone and IGF-I during growth and adulthood. The study of these transgenic animals can therefore provide important information directly relevant to human growth abnormalities such as gigantism and acromegaly. Radiographic or external examination of organ and skeletal proportions is an important step in the clinical evaluation of such growth disorders, as well as in the effectiveness of growth ormone therapies. The study of proportion changes in the transgenic mice may also contribute to both these health issues.

目的是使用转基因小鼠（MTrGH-Palmiter et al.， 1982年）作为一个实验模型的影响的研究 GH和IGF-I水平升高对器官和躯体生长的影响。 具体要分析的问题是， 器官和肌肉骨骼系统的形状变化， 巨大的转基因小鼠是由一般异速生长效应引起的 (i.e.其相对增长模式的扩展 正常大小同窝对照）或对 特定的靶器官和区域。 假设是 测试的是，所有的大小和内部比例的变化， 器官和肌肉骨骼系统在巨大的转基因 小鼠由一般大小因素或差异因素导致， 生长异速生长模式的扩展 正常大小的控制。 这一假设将用方法论的方法加以检验 从进化形态学的研究中得出， 适用于正常和异常生长。 这些方法 与个体发育异速生长（相对生长）、异时性有关 （尺寸、形状和定时参数的集成），以及 Wright（1932）的大小因素或影响的层次结构 （一般、团体和特别）。 这项研究直接关系到荷尔蒙的控制， 器官和骨骼比例在个体发育过程中， 异常生长。 转基因小鼠提供了重要的 研究长期暴露于 生长激素和IGF-I水平异常高， 成长与成年 对这些转基因动物的研究 因此可以提供直接相关的重要信息 人类发育异常，如自闭症， 肢端肥大症 器官X线或外部检查， 骨骼比例是临床上重要的一步 评估这种生长障碍，以及在 生长激素治疗的有效性。 研究 转基因小鼠的比例变化也可能有助于 这两个健康问题。