Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene.
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.
van Helden
Yvonne G J
YG
Department of Human and Animal Physiology, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands.
Heil
Sandra G
SG
van Schooten
Frederik J
FJ
Kramer
Evelien
E
Hessel
Susanne
S
Amengual
Jaume
J
Ribot
Joan
J
Teerds
Katja
K
Wyss
Adrian
A
Lietz
Georg
G
Bonet
M Luisa
ML
von Lintig
Johannes
J
Godschalk
Roger W L
RW
Keijer
Jaap
J
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
D019207:beta Carotene; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase