Isoprenoid biosynthesis is not compromised in a Zellweger syndrome mouse model.
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.
Vanhorebeek
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Laboratory of Clinical Chemistry, Katholieke Universiteit Leuven, Campus Gasthuisberg O/N, Herestraat 49, 3000, Leuven, Belgium.
Baes
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Declercq
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PE
D000818:Animals; D000831:Animals, Newborn; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D006579:Heterozygote; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism; D015211:Zellweger Syndrome / Q000378:metabolism*
D000074435:Peroxisome-Targeting Signal 1 Receptor; C000614265:Pex5 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D013729:Terpenes; D014451:Ubiquinone; D002784:Cholesterol; D013384:Succinate Cytochrome c Oxidoreductase