Publication Date:
2014-03-03
Description:
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 and high rate of perinatal lethality in these homozygous mutants. Although fro/fro mouse can be a useful tool to study many different aspects of SMPD3 functions, the perinatal lethality makes it difficult to generate 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 the current 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 the perinatal lethality. 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 . © 2014 Wiley Periodicals, Inc.
Topics:
Biology
,
Medicine
