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A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse

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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Figure 1: Abnormal mineralization in mutant mice and genetic localization of the Smpd3 locus.
Figure 2: Analysis of Smpd3 structure, expression and function.

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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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Correspondence to Jean-Louis Guénet.

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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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