Abstract
The mouse mutation fragilitas ossium (fro) leads to a syndrome of severe osteogenesis and dentinogenesis imperfecta with no detectable collagen defect. Positional cloning of the locus identified a deletion in the gene encoding neutral sphingomyelin phosphodiesterase 3 (Smpd3) that led to complete loss of enzymatic activity. Our knowledge of SMPD3 function is consistent with the pathology observed in mutant mice and provides new insight into human pathologies.
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Acknowledgements
We thank G. Langsley and K. McElreavey for critical reading of the manuscript and C. Kress for cell culture support. This work was partly supported by a Seed Grant from the Osteogenesis Imperfecta Foundation to C.P. and by a Fellowship from the CANAM to I.A. This paper is dedicated to the memory of Ritta Stanescu who, in collaboration with her husband Victor Stanescu, made many careful analyses aimed at a better understanding of the physiopathology of this mutation.
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Supplementary information
Supplementary Fig. 1
Sequences of the Smpd3 gene in the vicinity of the deletion breakpoint. (PDF 1035 kb)
Supplementary Fig. 2
Protein models of Smpd3 normal and mutant forms. (PDF 1020 kb)
Supplementary Table 1
Sequences of the primers that have been used for RT-PCR assays. (PDF 358 kb)
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Aubin, I., Adams, C., Opsahl, S. et al. A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nat Genet 37, 803–805 (2005). https://doi.org/10.1038/ng1603
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DOI: https://doi.org/10.1038/ng1603
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