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Publication : 0177 Functional studies of Osteoadherin by tissue-specific over-expression in mice

First Author  Rehn A Year  2007
Journal  Joint Scientific Meeting of BDSR and NOF Mgi Jnum  J:184577
Mgi Id  MGI:5424334 Citation  Rehn A, et al. (2007) 0177 Functional studies of Osteoadherin by tissue-specific over-expression in mice. Joint Scientific Meeting of BDSR and NOF
abstractText  Objectives: we sought to investigate functional properties of the small leucine-rich proteoglycan Osteoadherine (OSAD), a protein with restricted expression to beone and teeth. Since knock-out experiments have failed to show any associated phenotype in animals, our approach was to generate a transgenic mouse strain with tissue-specific expression of OSAD. Methods: an expression plasmid with OSAD cDNA under the control of the Osteocalcin promoter was generated and transgenic mouse lines were obtained by using the pronuclear injection technique. Positive transgenic animals were evaluated by gDNA PCR analysis with insert-specific primers and by western blotting. Bone density measurements of tibiae were performed by peripheral Quantitative Computed Tomography (pQCT) on tibiae from male animals at an age of 4 and 16 weeks. Mandibles were sectioned and stained with hematoxylin and eosin. Results: we selected for the clone with the strongest transgenic signal by PCR screening, and western blotting for the costruct specific c-Myc tag confirmed expression of the transgenic protein. Heterozygous mating produced a tg/wt offspring distribution according to Mendelian law. Tibiae and mandible ex vivo analysis revealed distinct phenotypical differences in bone and teeth mineral content and quality. Conclusion: we have managed to establish a transgenic mouse strain that over-expresses OSAD in a tissue-specific manner. The Mendelian distribution of offspring shows that the animals are fully fertile and that survival is not dependent on the expession of OSAD. Bone and tooth tissue analysis show a distinct phenotype, which however seems to diminish as the mice age. A possible mechanism could be that OSAD affects the cellular component of mineralized tissues in their ablility to deposit and maintain hydroxyapatite or collagen. Seq #25 - Mineralized Tissues Joint Scientific Meeting of BDSR and NOF (3rd - 5th April 2007), Durhan, England
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