Isoprenoid biosynthesis is not compromised in a Zellweger syndrome mouse model.

Abstract

Because several studies indicated that peroxisomes are important for the biosynthesis of isoprenoids, we wanted to investigate whether a reduced availability of isoprenoids could be one of the pathogenic factors contributing to the severe phenotype of the Pex5(-/-) mouse, a model for Zellweger syndrome. Total cholesterol was determined in plasma, brain and liver of newborn mice. In none of these tissues a significant difference was observed between Pex5(-/-) and wild type or heterozygous mice. The hepatic ubiquinone content was found to be even higher in Pex5(-/-) mice as compared to wild type or heterozygous littermates. To investigate whether the Pex5(-/-) fetuses are able to synthesise their own isoprenoids, fibroblasts derived from these mice were incubated with radiolabeled mevalonolactone as a substrate for isoprenoid synthesis. No significant difference was observed between the cholesterol production rates of Pex5(-/-) and normal fibroblasts. Our results show that there is no deficiency of isoprenoids in newborn Pex5(-/-) mice, excluding the possibility that a lack of these compounds is a determinant factor in the development of the disease state before birth.

• Authors: I Vanhorebeek, M Baes, P E Declercq
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1532 Issue 1-2 Pg. 28-36 (May 31 2001) ISSN: 0006-3002 [Print] Netherlands
• PMID: 11420171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peroxisome-Targeting Signal 1 Receptor
• Pex5 protein, mouse
• Receptors, Cytoplasmic and Nuclear
• Terpenes
• Ubiquinone
• Cholesterol
• Succinate Cytochrome c Oxidoreductase

Topics

• Animals
• Animals, Newborn
• Cholesterol (biosynthesis, metabolism)
• Disease Models, Animal
• Heterozygote
• Liver (metabolism)
• Mice
• Mice, Knockout
• Peroxisome-Targeting Signal 1 Receptor
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Succinate Cytochrome c Oxidoreductase (metabolism)
• Terpenes (metabolism)
• Ubiquinone (metabolism)
• Zellweger Syndrome (metabolism)