Generation of vascular smooth muscle specific Ubiad1 gene knockout mice and phenotype analysis

• Project/Area Number: 26460180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Osaka Shoin Women's University (2015-2016); Kobe Pharmaceutical University (2014)
• Principal Investigator: Tsugawa Naoko 大阪樟蔭女子大学, 健康栄養学部, 教授 (30207352)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ビタミンK / UBIAD1 / 血管特異的遺伝子欠損 / 血管平滑筋 / Transgelin-Cre / メナキノン4 / 血管石灰化

Outline of Final Research Achievements

UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme. To investigate the function of UBIAD1 in vascular smooth muscle cells, we attempted to generate vascular specific conditional Ubiad1 knockout mice (Ubiad1-V-KO). Ubiad1-V-KO was generated with conditional deletion of Ubiad1 gene in cells expressing the smooth muscle cell-specific protein SM22α. Ubiad1-V-KO were born according to Mendel's theory of heredity, however all Ubiad1-V-KO were died with pleural effusion at 6-8 weeks-old. Also, we confirmed that abnormality of aortic elastic fiber, ventricular myocardial hypoplasia, hypertension and decrease of heart rate in Ubiad1-V-KO.

Research Products

• [Journal Article] Nongenomic effects of 1α,25-dihydroxyvitamin D3 on cartilage formation deduced from comparisons between Cyp27b1 and Vdr knockout mice (2017)
  • Author(s): Y Hirota K Nakagawa S Mimatsu N Sawada T Sakaki N Kubodera M Kamao N Tsugawa Y Suhara T Okano
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 483 Issue: 1 Pages: 359-365
  • DOI: 10.1016/j.bbrc.2016.12.139
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between vitamin D status and serum parathyroid hormone concentration and calcaneal stiffness in Japanese adolescents: sex differences in susceptibility to vitamin D deficiency. (2016)
  • Author(s): Tsugawa N, Uenishi K, Ishida H, Ozaki R, Takase T, Minekami T, Uchino Y, Kamao M, Okano T.
  • Journal Title: J Bone Miner Metab. Volume: 34
  • Peer Reviewed
• [Journal Article] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015)
  • Author(s): Hirota Y, Nakagawa K, Sawada N, Okuda N, Suhara Y, Uchino Y, Kimoto T, Funahashi N, Kamao M, Tsugawa N, Okano T.
  • Journal Title: PLoS One. Volume: 10
  • NAID: 130007413127
  • Peer Reviewed / Open Access
• [Journal Article] Cardiovascular Diseases and Fat Soluble Vitamins: Vitamin D and Vitamin K. (2015)
  • Author(s): Tsugawa N
  • Journal Title: J Nutr Sci Vitaminol (Tokyo). Volume: 61 Pages: 170-172
  • NAID: 130005109894
• [Journal Article] Effects of Fok-I polymorphism in vitamin D receptor gene on serum 25-hydroxyvitamin D, bone-specific alkaline phosphatase and calcaneal quantitative ultrasound parameters in young adults. (2015)
  • Author(s): Tanabe R, Kawamura Y, Tsugawa N, Haraikawa M, Sogabe N, Okano T, Hosoi T, Goseki-Sone M.
  • Journal Title: Asia Pac J Clin Nutr. Volume: 24 Pages: 329-335
  • Peer Reviewed / Open Access
• [Journal Article] Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ＞＝60 ml/min/1.73 m2. (2015)
  • Author(s): Nakatani S, Nakatani A, Tsugawa N, Yamada S, Mori K, Imanishi Y, Ishimura E, Okano T, Inaba M.
  • Journal Title: Nephron. Volume: 130 Pages: 119-126
  • Peer Reviewed
• [Journal Article] High prevalence of vitamin D deficiency in patients with xeroderma pigmetosum-A under strict sun protection. (2015)
  • Author(s): Kuwabara A, Tsugawa N, Tanaka K, Uejima Y, Ogawa J, Otao N, Yamada N, Masaki T, Nishigori C, Moriwaki S, Okano T.
  • Journal Title: Eur J Clin Nutr. 2015 Volume: 69 Pages: 693-696
  • Peer Reviewed
• [Journal Article] Functional Characterization of the Vitamin K2 Biosynthetic Enzyme UBIAD1. (2015)
  • Author(s): Hirota Y, Nakagawa K, Sawada N, Okuda N, Suhara Y, Uchino Y, Kimoto T, Funahashi N, Kamao M, Tsugawa N, Okano T.
  • Journal Title: PLoS One Volume: 10
  • NAID: 130007413127
  • Peer Reviewed / Open Access
• [Journal Article] Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice. (2014)
  • Author(s): Nakagawa K, Sawada N, Hirota Y, Uchino Y, Suhara Y, Hasegawa T, Amizuka N, Okamoto T, Tsugawa N, Kamao M, Funahashi N, Okano T.
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed / Open Access
• [Presentation] The Elevation of Renal Renin Production Does Not Necessarily Correlate with Blood Pressure in Vitamin D Receptor Gene Knockout Mice Fed Hypocalcemia Rescue Diet. (2015)
  • Author(s): Naoko Tsugawa, Miku Wada, Kisato Kanao, Toshio Okano
  • Organizer: 2015 Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Seattle, USA
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] 異所性石灰化に伴う軟組織における骨芽細胞様形質の獲得とMatrix Gla Protein（MGP）発現の関係 (2015)
  • Author(s): 苫田紘佳、津川尚子、中村 拳、山本真由美、安田真央、中川公恵、岡野登志夫
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良
  • Year and Date: 2015-06-05