ALLOMETRIC GROWTH IN GIANT TRANSGENIC RODENTS

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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.