This research focuses on the investigation of the effects of variation in systemic growth hormones on craniofacial growth, dental size and occlusal patterns. Craniofacial proportion changes during growth will be determined in littermate control groups and five primary models of endocrine growth disturbance: 1) giant transgenic (MT-rGH and L-FABP-hGH) mice; 2) Little (lit/lit) dwarf mutant mice; 3) Snell (dw/dw) dwarf mutant mice; 4) Ames (df/df dwarf mutant mice; and 5) Pygmy (pg/pg) dwarf mutant mice. The general hypothesis to be tested in this research is that differences in craniofacial size and shape between the various experimental and control groups result from differential extension (in the transgenic giants) or truncation (in the mutant dwarfs) of the patterns of allometric growth observed in the respective control groups. Hypotheses also predict no change in tooth size or occlusal patterns in the experimental vs. control groups. The hypotheses will be tested through collection of an extensive suite of linear craniodental and mandibular dimensions, plus linear and angular radiographic measurements, in both crosssectional and longitudinal growth series. Analyses will be based on a tripartite separation of size and proportion differences into factors that may be described as general (due to overall body growth and inherent allometric patterns), group (due to regional size differences and allometric patterns) and special (reflecting localized growth dissociations independent of regional or general size influences. The recent successful production of biosynthesized growth hormone will greatly increase the frequency of clinical intervention and therapy in individuals with endocrine growth disturbances. The specific ramifications of GH administration for general and local patterns of craniofacial growth are of great relevance to orthodontists, maxillo-facial surgeons and other clinicians involved in manipulating and predicting aspects of facial growth. Comparatively little research investigating the specific effects of endocrinopathies on craniofacial growth and occlusion has been completed, and none of the five important murine models to be examined in this proposed work have ever been rigorously studied in this regard, let alone systematically compared. This research will contribute to our understanding of this important area. It will also provide a necessary and valuable foundation for future research on these murine models of endocrinopathy and craniofacial biology, including more detailed analyses of cell kinetics, localized patterns of resorption and deposition, and the specific effects of experimental hormone therapy.
