Establishment of congenic strains of mice carrying a genomic interval which regulates the onset of osteoporotic phenotype.

建立携带调节骨质疏松表型发作的基因组区间的小鼠同源品系。

• 批准号: 11470308
• 负责人: TSUBOYAMA Tadao
• 金额: $ 3.97万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470308/
• 关键词: osteoporosis; animal model; genetic background; QTL; SAM; congenic strain; polygene

Previously, we identified two quantitative trait loci (QTLs) specifying the peak relative bone mass on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains, SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2. In this study, we constructed interval-specific congenic strains in order to dissect the polygenic trait into single gene factors. By seven consecutive backcrosses and intercrossmating of the N7mice, four congenic strains (P2.P6-pbd1^a, P2.P6-pbd2^a, P6.P2-pbd1^b, P6.P2-pbd2^b) were produced. P2.P6-pbd1^a and P2.P6-pbd2^a had a SAMP6-derived 48cM interval from Chr 11 and a SAMP6-derived 15cM interval from Chr 13, respectively, on a SAMP2-derived background. To the contrary, P6.P2-pbd1^b and P6.P2-pbd2^b had a SAMP2-derived 32cM interval from Chr 11 and SAMP2-derived 15cM interval from Chr 13, respectively, on a SAMP6-derived background. Microdensitometry, dual-energy X-ray absorptiometry, and peripheral quantitative computed tomography revealed lower bone density in P2.P6-pbd1^a and P2.P6-pbd2^a than in the background SAMP2 mice. These measurements showed lower bone density in P6.P2-pbd1^b and P6.P2-pbd2^b than in the background SAMP6 mice. These results confirmed the existence of loci regulating bone density on Chr 11 and Chr 13 in the SAM stains.

在此之前，我们在SAMP2和SAMP6两个品系的小鼠中通过区间作图确定了两个数量性状基因座(QTL)，该QTL指定了染色体(CRAS)11和13上的峰值相对骨量。后者是一种已建立的老年性骨质疏松症小鼠模型，其峰值相对骨量明显低于SAMP2。在本研究中，我们构建了区间特异的同源品系，以将多基因性状分解为单基因因素。对N7小鼠连续7次回交、杂交，获得4个同源品系(P2.P6-pbd1^a、P2.P6-pbd2^a、P6.P2-pbd1^b、P6.P2-pbd2^b)。在SAMP2背景下，P2.P6-pbd1^a和P2.P6-pbd2^a分别具有SAMP6起源于Chr 11的48 cM间隔和SAMP6起源于Chr 13的15 cM间隔。相反，P6.P2-pbd1^b和P6.P2-pbd2^b在SAMP6起源的背景下，分别有一个SAMP2起源于Chr 11的32 cM间隔和SAMP2起源于Chr 13的15 cM间隔。显微密度测量、双能X射线吸收测量和外周定量计算机断层扫描显示，P2.P6-pbd1^a和P2.P6-pbd2^a的骨密度低于背景SAMP2小鼠。这些测量显示，P6.P2-pbd1^b和P6.P2-pbd2^b的骨密度低于背景SAMP6小鼠。这些结果证实了在SAM染色中存在Chr 11和Chr 13上的骨密度调节基因。

项目成果

清水基行,坪山直生,松下睦,笠井宗一郎,中村孝志,細川昌則: "老化促進モデルマウスSAMを用いた第11骨量制御遺伝子座の解析"Osteoporosis Japan. 9(2)(in press). (2000)

Motoyuki Shimizu、Nao Tsuboyama、Mutsumi Matsushita、Soichiro Kasai、Takashi Nakamura、Masanori Hosokawa：“使用加速老化模型小鼠 SAM 分析第 11 个骨量控制基因位点” Osteoporosis Japan 9(2)（出版中）（2000 年）。

M.Shimizu,T.Tsuboyama,M.Matsushita,S Kasai: "Identification of quantitative trait loci that control low peak bone mass using a spontaneously osteoporotic mouse strain, SAMP6"J.Bone Miner Metab. 17(4). 313-314 (1999)

M.Shimizu、T.Tsuboyama、M.Matsushita、S Kasai：“使用自发性骨质疏松小鼠品系 SAMP6 识别控制低峰骨量的数量性状位点”J.Bone Miner Metab。

M.Shimizu: "Indentification of quantitative trait loci that control low peak bone mass using a spontaneously osteoporotic mouse strain, SAMP6"J. Bone Miner Metab,. 17(4). 313-314 (1999)

M.Shimizu：“使用自发性骨质疏松小鼠品系 SAMP6 识别控制低峰骨量的数量性状基因座”J。

M.Shimizu, M.Matsushita, T.Tsuboyama T.Nakamura, M.Hosokawa, and N.Shimizu: "Developmental osteopenia of Senescence-Accelerated Mouse (SAM)(in Japanese)."THE BONE.. 13(3). 69-72 (1999)

M.Shimizu、M.Matsushita、T.Tsuboyama T.Nakamura、M.Hosokawa 和 N.Shimizu：“衰老加速小鼠 (SAM) 的发育性骨质减少（日语）。”THE BONE.. 13(3)。

M.Shimizu, T.Tsuboyama, M.Matsushita, S.Kasai, T.Nakamura, M.Hosokawa, N.Shimizu, and K.Higuchi.: "Analysis of loci that control peak bone mass using SAM strains (in Japanese)."Osteoporosis Japan.. Vol.8 No.1. 248-250 (2000)

M.Shimizu、T.Tsuboyama、M.Matsushita、S.Kasai、T.Nakamura、M.Hosokawa、N.Shimizu 和 K.Higuchi.：“使用 SAM 菌株控制峰值骨量的基因座分析（日语）