Molecular basis of intracellular cholesterol regulation in the maturation of canine erythroid cells.
| Project/Area Number |
25660234
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Veterinary medical science
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| Research Institution | Hokkaido University |
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Principal Investigator |
SATO Kota 北海道大学, (連合)獣医学研究科, 准教授 (50283974)
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| Co-Investigator(Kenkyū-buntansha) |
INABA Mutsumi 北海道大学, 大学院獣医学研究科, 教授 (00183179)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | コレステロール / 赤芽球 / 分化成熟 / 赤血球 / 犬 / 赤芽球成熟 / 遺伝性疾患 |
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| Outline of Final Research Achievements |
Dog red cells show low intracellular K+ (LK) phenotype; however, some Japanese dogs have high intracellular K+ (HK) red cells which exhibit characteristics similar to reticulocytes. In the present study, we determined that TSPO2 was the candidate gene for the HK phenotype by genome-wide association study. HK dogs possessed two different mutant alleles in TSPO2 that resulted in amino acid substitutions: C40Y and the triple mutations V89F/ΔF98/T120I (VFT). Analysis of genomic DNA demonstrated that the dogs possessing HK red cells were homozygotes for the C40Y allele or compound heterozygotes for the C40Y and the VFT allele. In stable transfectants of K562 cells, the intracellular deposition of free cholesterol was evident in K562 cells expressing wild-type TSPO2 but not in cells expressing C40Y or VFT mutants. These findings suggest that impaired cholesterol metabolism during erythroid development and maturation are involved in the molecular cause of the HK red cell phenotype.
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Report
(3 results)
Research Products
(6 results)
