Isoprenoid biosynthesis is not compromised in a Zellweger syndrome mouse model

Because several studies indicated that peroxisomes are important for the bi osynthesis of isoprenoids, we wanted to investigate whether a reduced avail ability of isoprenoids could be one of the pathogenic factors contributing to the severe phenotype of the Pex5(-/-) mouse, a model for Zellweger syndr ome. Total cholesterol was determined in plasma, brain and liver of newborn mice. In none of these tissues a significant difference was observed betwe en Pex(5-/-) and wild type or heterozygous mice. The hepatic ubiquinone con tent was found to be even higher in Pex(5-/-) mice as compared to wild type or heterozygous littermates. To investigate whether the Pex(5-/-) fetuses an able to synthesise their own isoprenoids, fibroblasts derived from these mice were incubated with radiolabeled mevalonolactone as a substrate for i soprenoid synthesis. No significant difference was observed between the cho lesterol production rates of Pex(5-/-) and normal fibroblasts. Our results show that then is no deficiency of isoprenoids in newborn Pex(5-/-) mice, e xcluding the possibility that a lack of these compounds is a determinant fa ctor in the development of the disease state before birth. (C) 2001 Elsevie r Science B.V. All rights reserved.