Ilse Vanhorebeek، نويسنده , , Myriam Baes، نويسنده , , Peter E. Declercq، نويسنده ,

1601765

Isoprenoid biosynthesis is not compromised in a Zellweger syndrome mouse model

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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.

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Zellweger syndrome , isoprenoid , cholesterol , peroxisome

Studia Iranica

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