title: Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene.
abstract: Beta-carotene 15,15'-monooxygenase 1 knockout (Bcmo1 (-/-)) mice accumulate beta-carotene (BC) similarly to humans, whereas wild-type (Bcmo1 (+/+)) mice efficiently cleave BC. Bcmo1 (-/-) mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis. Bcmo1 (-/-) mice receiving control diet had increased expression of inflammatory genes as compared to BC-supplemented Bcmo1 (-/-) mice and Bcmo1 (+/+) mice that received either control or BC-supplemented diets. Differential gene expression in Bcmo1 (-/-) mice was confirmed by real-time quantitative PCR. Histochemical analysis indeed showed an increase in inflammatory cells in lungs of control Bcmo1 (-/-) mice. Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1 (-/-) mice. This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1.
authors.affiliation: Department of Human and Animal Physiology, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands.
authors.forename: Yvonne G J
authors.initials: YG
authors.lastname: van Helden
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Heil
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Evelien
authors.initials: E
authors.lastname: Kramer
authors.forename: Susanne
authors.initials: S
authors.lastname: Hessel
authors.forename: Jaume
authors.initials: J
authors.lastname: Amengual
authors.forename: Joan
authors.initials: J
authors.lastname: Ribot
authors.forename: Katja
authors.initials: K
authors.lastname: Teerds
authors.forename: Adrian
authors.initials: A
authors.lastname: Wyss
authors.forename: Georg
authors.initials: G
authors.lastname: Lietz
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Bonet
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
authors.forename: Jaap
authors.initials: J
authors.lastname: Keijer
mesh_terms: D000818:Animals; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D050356:Lipid Metabolism / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019207:beta Carotene / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019207:beta Carotene; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase