Parsons Kelly K, Maeda Nobuyo, Yamauchi Mitsuo, Banes Albert J, Koller Beverly H
Dept. of Genetics, Univ. of North Carolina at Chapel Hill, 4341 MBRB, Chapel Hill, NC 27599, USA.
Am J Physiol Endocrinol Metab. 2006 Jun;290(6):E1131-9. doi: 10.1152/ajpendo.00339.2005. Epub 2005 Dec 13.
The mouse has become the most important model organism for the study of human physiology and disease. However, until the recent generation of mice lacking the enzyme gulanolactone oxidase (Gulo), the final enzyme in the ascorbic acid biosynthesis pathway, examination of the role of ascorbic acid in various biochemical processes using this model organism has not been possible. In the mouse, similar to most mammals but unlike humans who carry a mutant copy of this gene, Gulo produces ascorbic acid from glucose. We report here that, although ascorbic acid is essential for survival, its absence does not lead to measurable changes in proline hydroxylation. Vitamin C deficiency had no significant effect on the hydroxylation of proline and collagen production during tumor growth or in angiogenesis associated with tumor or mammary gland growth. This suggests that factors other than ascorbic acid can support proline hydroxylation and collagen synthesis in vivo. Furthermore, the failure of Gulo-/- mice to thrive on a vitamin C-deficient diet therefore suggests that ascorbic acid plays a critical role in survival other than the maintenance of the vasculature.
小鼠已成为研究人类生理学和疾病的最重要模式生物。然而，直到最近培育出缺乏古洛糖酸内酯氧化酶（Gulo）（抗坏血酸生物合成途径中的最后一种酶）的小鼠，才能够利用这种模式生物研究抗坏血酸在各种生化过程中的作用。在小鼠中，与大多数哺乳动物一样，但与携带该基因突变副本的人类不同，Gulo可利用葡萄糖生成抗坏血酸。我们在此报告，尽管抗坏血酸对生存至关重要，但其缺失并不会导致脯氨酸羟化发生可测量的变化。维生素C缺乏对肿瘤生长过程中或与肿瘤或乳腺生长相关的血管生成过程中的脯氨酸羟化和胶原蛋白生成没有显著影响。这表明除抗坏血酸外的其他因素可以在体内支持脯氨酸羟化和胶原蛋白合成。此外，Gulo基因敲除小鼠在缺乏维生素C的饮食条件下无法茁壮成长，这表明抗坏血酸在维持血管系统之外的生存中起着关键作用。
