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 .