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Inducible transient expression of Smpd3 prevents early lethality in fro/fro mice
Author(s) -
Alebrahim Sharifa,
Khavandgar Zohreh,
Marulanda Juliana,
Murshed Monzur
Publication year - 2014
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.22765
Subject(s) - biology , embryo , gene expression , phenotype , gene , knockout mouse , microbiology and biotechnology , genetics
Summary 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. genesis 52:408–416, 2014. © 2014 Wiley Periodicals, Inc.