Inducible transient expression of Smpd3 prevents early lethality in fro/fro mice. Issue 5 (13th March 2014)

• Record Type: Journal Article
• Authors: Alebrahim, Sharifa; Khavandgar, Zohreh; Marulanda, Juliana; Murshed, Monzur
• Is Part Of: Genesis. Volume 52:Issue 5(2014:May)
• Page Start: 408
• Page End: 416
• Publication Date: 2014-03-13
• Subjects: Developmental genetics -- Periodicals; Genetics -- Periodicals; Developmental biology -- Periodicals; Embryology -- Periodicals; Genetic regulation -- Periodicals; 576.5
• DOI: 10.1002/dvg.22765
• Languages: English
• ISSNs: 1526-954X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Sphingomyelin phosphodiesterase 3 (SMPD3) is a pleiotropic lipid metabolizing enzyme involved in multiple physiological processes. A deletion mutation in the murine <italic>Smpd3</italic> gene called <italic>fragilitas ossium (fro</italic>) leads to severe skeletal abnormalities in the developing <italic>fro/fro</italic> embryos. Although <italic>fro/fro</italic> 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 <italic>fro/fro</italic> mice survive beyond the perinatal stage. In this study, we used the "Tet‐On" inducible gene expression system to express <italic>Smpd3</italic> transiently in <italic>fro/fro;ROSA‐rtTA;TRE‐Smpd3</italic> embryos on the C57BL/6 background. This induced <italic>Smpd3</italic> expression corrected all the skeletal abnormalities in these embryos and prevented their early death. However, induction of <italic>Smpd3</italic> expression in the adolescent <italic>fro/fro;ROSA‐rtTA;TRE‐Smpd3</italic> 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.</p> </abstract>