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Am J Physiol Endocrinol Metab 290: E1131-E1139, 2006. First published December 13, 2005; doi:10.1152/ajpendo.00339.2005
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Ascorbic acid-independent synthesis of collagen in mice

Kelly K. Parsons,1 Nobuyo Maeda,2 Mitsuo Yamauchi,3 Albert J. Banes,4 and Beverly H. Koller1

Departments of 1Genetics, 2Pathology, 3Periodontology, and 4Orthopaedics, The University of North Carolina Chapel Hill, Chapel Hill, North Carolina

Submitted 26 July 2005 ; accepted in final form 12 December 2005

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.

ascorbic acid; collagen; angiogenesis; prolyl hydroxylase



Address for reprint requests and other correspondence: B. H. Koller, Dept. of Genetics, Univ. of North Carolina at Chapel Hill, 4341 MBRB, Chapel Hill, NC 27599 (e-mail: treawouns{at}aol.com)




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