This proposal aims to investigate the role of perlecan in the skeletal system using the SJ-C1532Y mouse as a model for Schwartz-Jampel syndrome type 1 A. Before this can be initiated, the mouse must first be evaluated for its usefulness as an appropriate model. Once established to mimic the human condition, SJC1532Y mice will be used to clarify the mechanism of Schwartz-Jampel disease onset and progression with a focus on the skeletal system. Because SJ patients suffer from numerous craniofacial abnormalities in addition to defects in bone arising via endochondrial ossification, it is likely that proper amount and form of perlecan is critical for efficient growth factor signaling and endochondrial bone formation. The SJ-C1532Y mice will enable these questions to be addressed and may serve to aid in the development of future methods of disease intervention. In the event that the SJ-C1532Y mice do not model SJ syndrome, an alternative approach will be used to study the role of perlecan in skeletal formation and maintenance. The ability of perlecan domain I alone to rescue the perlecan null phenotype in cartilage will be addressed using transgenic mice, a project related to the disease dysssegmental dysplasia, Silverman-Handmaker type.
| Rodgers, Kathryn D; Sasaki, Takako; Aszodi, Attila et al. (2007) Reduced perlecan in mice results in chondrodysplasia resembling Schwartz-Jampel syndrome. Hum Mol Genet 16:515-28 |
