Use of Vitamin K-deficient AIN-93 Diet is an Effective Approach to Create Subclinical Vitamin K Deficiency in C57BL/6 Mice

Abstract

Despite the popularity of genetically modified mouse models for mechanistic studies of human disease, little is known about the vitamin K requirements for mice. In the current study, we performed a small pilot time course study to determine the least amount of time required to reduce tissue concentrations of vitamin K without causing clinical signs of deficiency, such as abnormal bleeding. Female C57BL/6 mice were acclimated with AIN-93 G diet (903.5±26.5μg phylloquinone/kg diet) for 1 wk and subsequently fed a vitamin K-deficient AIN-93 G diet (21.4±3.0 μg phylloquinone/kg diet) for 0d (0D group; n=3), 7d (7D group; n=3), 14d (14D group; n=3) and 28d (28D group; n=3) while limiting coprophagy. Phylloquinone and menaquinone-4 (MK-4) concentrations were measured in serum, liver, kidney, brain, pancreas, and body fat (omental). Compared to 0D group, there was a reduction of vitamin K concentrations in all analyzed tissues within 7d (P<0.05), with the exception of body fat. In the 28D group, vitamin K was not detectable in mouse liver, yet there were no clinical signs of vitamin Kdeficiency, including bleeding. In summary, a vitamin K deficient diet can be used to induce low vitamin K tissue concentrations within 7d.