The role of β‐carotene‐15,15′‐oxygenase (CMO1) during mammalian embryonic development

Abstract

β‐carotene is the best‐known vitamin A precursor. By the action of β‐carotene‐15,15′‐oxygenase (CMO1), one molecule of β‐carotene can be cleaved symmetrically, ultimately resulting in the formation of two molecules of retinol. Vitamin A is essential for embryonic development. In order to meet vitamin A requirements, the mammalian embryo relies on maternal circulating retinoids (vitamin A and its derivatives). We previously showed that, upon maternal dietary vitamin A deprivation, normal embryonic development is impaired in mice lacking retinol‐binding protein (RBP), the sole specific carrier for retinol in the bloodstream. To investigate the relationship between carotenoid and retinoid metabolism during development, we generated a mouse strain that lacks both CMO1 and RBP (CMO1−/−RBP−/−). We show that CMO1−/−RBP−/− mice are viable and fertile when maintained on a vitamin A‐sufficient diet. However, E14.5 embryos from CMO1−/−RBP−/− dams bred on a vitamin A‐deficient diet are malformed, and the severity of malformations is greater than those seen in RBP−/− embryos. No differences in circulating retinoids levels were observed between CMO1−/−RBP−/− and RBP−/− dams. Also, embryonic development in CMO1−/− mice is normal. We are now investigating the reasons for the embryonic phenotype of the CMO1−/−RBP−/− mice to elucidate the physiological role played by CMO1 and β‐carotene during development.