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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Forlino, A. & Marini, J.C. Mol. Genet. Metab. 71, 225–232 (2000).
Sillence, D.O., Senn, A. & Danks, D.M. J. Med. Genet. 16, 101–116 (1979).
Glorieux, F.H. et al. J. Bone Miner. Res. 15, 1650–1658 (2000).
Glorieux, F.H. et al. J. Bone Miner. Res. 17, 30–38 (2002).
Ward, L.M. et al. Bone 31, 12–18 (2002).
Guénet, J.-L., Stanescu, R., Maroteaux, P. & Stanescu, V. J. Hered. 72, 440–441 (1981).
Muriel, M.P. et al. Bone 12, 241–248 (1991).
Sillence, D.O., Ritchie, H.E., Dibbayawan, T., Eteson, D. & Brown, K. Am. J. Med. Genet. 45, 276–283 (1993).
Goni, F.M. & Alonso, A. FEBS Lett. 531, 38–46 (2002).
Grey, A. et al. Calcif. Tissue Int. 74, 542–550 (2004).
Takeda, H. et al. FEBS Lett. 422, 255–258 (1998).
Wu, L.N., Genge, B.R., Kang, M.W., Arsenault, A.L. & Wuthier, R.E. J. Biol. Chem. 277, 5126–5133 (2002).
Goldberg, M. & Boskey, A.L. Prog. Histochem. Cytochem. 31, 1–187 (1996).
Auge, N. et al. J. Biol. Chem. 273, 12893–12900 (1998).
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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