S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Master's Degree_의학과)
The effect of ascorbic acid deficiency on bone formation in Gulo knock out mice
Gulo 유전자 적중 생쥐에서의 아스코르빈산 결핍이 골형성에 미치는 영향
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2012. 8. 이왕재.
- L-gulono-γ-lactone oxidase (Gulo) is an essential enzyme in the synthesis of ascorbic acid from glucose. It is known that gulo is mutated in humans and certain primates. Gulo (-/-) mice are a useful animal model of human scurvy when they are raised under an ascorbic acid-deficient condition, since Gulo (-/-) mice have a defect in the expression of the gulo gene. Based on previous findings on bone abnormalities, including multiple chondrocostal junction fractures in Gulo (-/-) mice upon ascorbic acid insufficiency, the specific factors at work are investigated on the present study. At 4 weeks after ascorbic acid withdrawal, a definite loss of weight was found in ascorbic acid-insufficient Gulo (-/-) mice. Interestingly, the plasma level of osteocalcin, which is secreted solely by osteoblasts and is thought to play a role in the metabolic regulation of bone, was dramatically decreased in ascorbic acid-insufficient Gulo (-/-) mice 3 weeks after ascorbic acid withdrawal. In addition, it was no longer detected at 4 weeks after ascorbic acid withdrawal. The tibia weight of the ascorbic acid-sufficient Gulo (-/-) mice was significantly higher than the other three groups. The trabecular bone volume was decreased near the growth plate. Moreover, we found a significant decrease in the trabecular bone attachment to the growth plate in ascorbic acid-insufficient Gulo (-/-) mice at 3 or 4 weeks after ascorbic acid withdrawal. Taken together, there are severe defects in normal bone formation as the result of ascorbic acid insufficiency, and this effect is closely related to a decrease in the osteocalcin level.