Inducible transient expression of Smpd3 prevents early lethality in fro/fro mice.
Genesis
; 52(5): 408-16, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24585429
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Osteogénesis Imperfecta
/
Esfingomielina Fosfodiesterasa
/
Genes Letales
Límite:
Animals
Idioma:
En
Año:
2014
Tipo del documento:
Article