Generation and characterization of genetically-altered mice lacking a novel vitamin K2 synthesis enzyme Ubiad1

研究表明，组织维生素K2起源于口服维生素K1，其机制包括维生素K1在肠道中释放维生素K3，然后通过肠系膜淋巴系统和血液循环将维生素K3输送到组织中，然后被组织中未知的氧化还原酶还原，并通过前置化酶Ubiad1转化为维生素K2。为了研究ubiad1的功能，我们试图通过基因靶向产生缺乏ubiad1的小鼠，但发现缺乏ubiad1的小鼠胚胎无法存活超过胚胎期7.5天。通过将Ubiad1 flox/flox小鼠与nesting - cre表达小鼠、Osterix-Cre表达小鼠或Synapsin-Cre表达小鼠杂交，我们成功地培养出了造血和神经组织特异性、骨特异性或神经元特异性的Ubiad1缺陷小鼠。

It was demonstrated that tissue vitamin K2 originates from oral vitamin K1 by a mechanism that involves the release of vitamin K3 from vitamin K1 in the intestine followed by delivery of vitamin K3 through the mesenteric lymphatic system and blood circulation to tissues, and then reduced by an unknown redox enzyme in the tissues and converted into vitamin K2 by the prenylating enzyme Ubiad1. To investigate the function of ubiad1, we attempted to generate mice lacking Ubiad1 by gene targeting, but it was found that Ubiad1-deficient mouse embryos failed to survive beyond embryonic day 7.5. We have succeeded in generating hematopoietic and nerve tissue -specific, bone specific- or neuron-specific Ubiad1-deficient mice by intercrossing Ubiad1 flox/flox mice with Nestin-Cre expressing mice, Osterix-Cre expressing mice or Synapsin-Cre expressing mice.