BMD regulation on mouse distal chromosome 1, candidate genes, and response to ovariectomy or dietary fat.
BMD regulation on mouse distal chromosome 1, candidate genes, and response to ovariectomy or dietary fat.
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DOI：
10.1002/jbmr.200
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发表时间：
2011-01
影响因子：
6.2
通讯作者：
Donahue, Leah Rae
中科院分区：
文献类型：
--
作者：
Beamer, Wesley G.;Shultz, Kathryn L.;Coombs, Harold F., III;DeMambro, Victoria E.;Reinholdt, Laura G.;Ackert-Bicknell, Cheryl L.;Canalis, Ernesto;Rosen, Clifford J.;Donahue, Leah Rae
小鼠1号染色体远端（Chr 1）含有调节骨矿物质密度（BMD）的数量性状位点（qtl），与人类染色体1q具有保守的同源性。本文的目的是绘制小鼠远端Chr 1区域，并确定负责雌性骨密度调节的基因。我们使用x射线密度仪[即双能x射线吸收仪（DXA），微计算机断层扫描（µCT）和外周定量计算机断层扫描（pQCT）]对一组由C57BL/6BmJ （B6/Bm）和C3H/HeJ （C3H）小鼠构建的巢式同源菌株进行表型分析，以绘制与BMD QTL相关的区域。当存在C3H等位基因时，临界区域的间隔减少到0.152 Mb，这有助于增加骨密度。组织形态学和成骨细胞培养表明，在这个关键区域有C3H等位基因的小鼠品系中，成骨细胞活性的增加与骨密度的增加有关。该区域包含两个基因，Aim2与细胞质dsDNA结合导致细胞凋亡，AC084073.22是一个功能未知的预测基因。卵巢切除术导致B6/Bm祖细胞和三个同源菌株的骨质流失，而不管关键BMD区域存在哪些等位基因。高脂肪饮食处理（被认为抑制小鼠骨密度的远端Chr 1 QTL）在携带AIM2和AC084073.22基因的关键0.152 Mb中携带C3H等位基因的基因中没有诱导骨质流失。全骨关键基因表达研究显示，携带B6/Bm与C3H等位基因的菌株AC084073.22表达差异，而携带Aim2的菌株无差异。综上所述，我们的数据表明，成骨细胞是基因作用的细胞靶点，AC084073.22是小鼠Chr 1远端区域雌性BMD调控的最佳候选基因。©2011美国骨与矿物研究学会。
The distal end of mouse chromosome 1 (Chr 1) harbors quantitative trait loci (QTLs) that regulate bone mineral density (BMD) and share conserved synteny with human chromosome 1q. The objective of this article was to map this mouse distal Chr 1 region and identify gene(s) responsible for BMD regulation in females. We used X-ray densitometry [ie, dual-energy X-ray Absorptiometry (DXA), micro–computed tomography (µCT), and peripheral quantitative computed tomography (pQCT)] to phenotype a set of nested congenic strains constructed from C57BL/6BmJ (B6/Bm) and C3H/HeJ (C3H) mice to map the region associated with the BMD QTL. The critical region has been reduced to an interval of 0.152 Mb that contributes to increased BMD when C3H alleles are present. Histomorphometry and osteoblast cultures indicated that increased osteoblast activity was associated with increased BMD in mouse strains with C3H alleles in this critical region. This region contains two genes, Aim2, which binds with cytoplasmic dsDNA and results in apoptosis, and AC084073.22, a predicted gene of unknown function. Ovariectomy induced bone loss in the B6/Bm progenitor and the three congenic strains regardless of the alleles present in the critical BMD region. High dietary fat treatment (thought to suppress distal Chr 1 QTL for BMD in mice) did not induce bone loss in the congenics carrying C3H alleles in the critical 0.152 Mb carrying the AIM2 and AC084073.22 genes. Gene expression studies in whole bone of key congenics showed differential expression of AC084073.22 for strains carrying B6/Bm versus C3H alleles but not for Aim2. In conclusion, our data suggest that osteoblasts are the cellular target of gene action and that AC084073.22 is the best candidate for female BMD regulation in the distal region of mouse Chr 1. © 2011 American Society for Bone and Mineral Research.
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影响因子：
6.2
作者：
Beamer, Wesley G.;Shultz, Kathryn L.;Rosen, Clifford J.
通讯作者：
Rosen, Clifford J.
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
影响因子：
5.8
作者：
Reed, BY;Gitomer, WL;Pak, CYC
通讯作者：
Pak, CYC
影响因子：
6.2
作者：
Ioannidis, John P. A.;Ng, Mandy Y.;Ralston, Stuart H.
通讯作者：
Ralston, Stuart H.
影响因子：
5.8
作者：
Koller, DL;Econs, MJ;Foroud, T
通讯作者：
Foroud, T