title: Inducible transient expression of Smpd3 prevents early lethality in fro/fro mice.
abstract: Sphingomyelin phosphodiesterase 3 (SMPD3) is a pleiotropic lipid metabolizing enzyme involved in multiple physiological processes. A deletion mutation in the murine Smpd3 gene called fragilitas ossium (fro) leads to severe skeletal abnormalities in the developing fro/fro embryos. Although fro/fro mice can be useful to study many different aspects of SMPD3 functions, their perinatal lethality makes it difficult to generate a sufficient number of mice for controlled studies. In fact, on the C57BL/6 genetic background, none of the fro/fro mice survive beyond the perinatal stage. In this study, we used the "Tet-On" inducible gene expression system to express Smpd3 transiently in fro/fro;ROSA-rtTA;TRE-Smpd3 embryos on the C57BL/6 background. This induced Smpd3 expression corrected all the skeletal abnormalities in these embryos and prevented their early death. However, induction of Smpd3 expression in the adolescent fro/fro;ROSA-rtTA;TRE-Smpd3 mice was not sufficient to correct the defects in trabecular bone mineralization and the impaired growth of the long bones. This novel mouse model will be a useful tool to study SMPD3 biology in vivo.
authors.affiliation: Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Sharifa
authors.initials: S
authors.lastname: Alebrahim
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Khavandgar
authors.forename: Juliana
authors.initials: J
authors.lastname: Marulanda
authors.forename: Monzur
authors.initials: M
authors.lastname: Murshed
mesh_terms: D000818:Animals; D004318:Doxycycline / Q000494:pharmacology; D017353:Gene Deletion; D015870:Gene Expression; D005804:Genes, Lethal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects; D010013:Osteogenesis Imperfecta / Q000196:embryology* / Q000235:genetics; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics* / Q000378:metabolism*
chemical_list: C491483:Smpd3 protein, mouse; D013108:Sphingomyelin Phosphodiesterase; D004318:Doxycycline
keywords: SMPD3; fro mutation; skeletal development; transgenic model; “Tet-On” system