Identification of quantitative trait loci specifying the onset of osteoporosis using a murine model.
| Project/Area Number |
09470316
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TSUBOYAMA Tadao Kyoto University, Department of Orthopaedic Surgery, Lecturer, 医学研究科, 講師 (90261221)
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| Co-Investigator(Kenkyū-buntansha) |
SHIGENO Chohei Kyoto University, Department of Orthopaedic Surgery, Assistant Professor, 医学研究科, 助手 (30170864)
HOSOKAWA Masanori Kyoto University, Institute for Frontier Medical Sciences Associate Professor, 再生医科学研究所, 助教授 (00127135)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥11,800,000 (Direct Cost: ¥11,800,000)
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| Keywords | Osteoporosis / Animal model / Genetic Background / QTL analysis |
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| Research Abstract |
The whole genome scan for quantitative trait loci (QTLs) specifying peak bone mass was performed with the F2 intercrosses of SAMP6, an established murine model of senile osteoporosis exhibiting a significantly lower peak bone mass, and SAMP2, exhibitinga higher peak bone mass. The bone masses of mice femurs were assayed photometrically using microdensitometry in 488 F2 progeny at 4 months of age, when the animals were reaching peak bone mass. Genetic markers were typed at 90 loci spanning all chromosomes except the Y.By interval mapping of 246 male F2 mice, two loci were identified with significant linkage to peak bone mass, one on chromosome 11 with a maximum lod score of 10.8 (22.2% of the total variance), and another on chromosome 13 with a maximum lod score of 5.8 (10.0%). Another locus on the X chromosome was suggestive of a QTL, We found no differences between SAMP6 and SAMP2 by sequencing genomic regions of G-CSF and a part of cDNA of chondroadherinin, which are candidate genes influencing low peak bone mass. We are constructing interval-specific congenic mice carrying appropriate SAMP6 and SAMP2 regions in order to refine the genetic locations of these QTLs. By cross-mating each congenic strain with parental strains and finding out the progenies that have a recombination within the putative QTL region detected in this study, it will be possible to make a high-resolution map and contract the QTL region. At present, we have established each N7 generation and homozygous mice by intercross-mating the N7 miceon Chr. 11, 13 and the X.These findings should be useful to elucidate the genetics of osteoporosis.
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Report
(3 results)
Research Products
(10 results)
