Opg-KO

品系全名

B6.129S-Tnfrsf11btm1Smoc

目录号

NM-KO-00004

品系状态

活体

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品系描述

骨质疏松症是一种全身骨代谢障碍疾病，是产生骨痛、驼背、身材变矮、骨折、骨坏死、致残的内在原因，以中老年人为高发人群，是影响中老年人群身体健康和生活质量的杀手之一。骨保护素（Osteoprotegerin，OPG）又称为破骨细胞抑制因子(OCIF)，临床研究表明OPG基因的多态性和骨密度相关。 骨保护素Opg（由Tnfrsf11b基因编码）敲除小鼠模型（简称“骨质疏松小鼠”）具有明确的骨质疏松症状，纯合子小鼠在1月龄时，已经出现骨丢失现象，而随着年龄的增加，在2-3月龄骨丢失更加显著。观察H.E染色的骨切片，在2-3月龄纯合子小鼠皮质骨则破骨细胞形成的陷窝明显增多,骨小梁数目减少，连接性下降。 该模型可以为“人类骨质疏松症”治疗药物的筛选和评价、骨质疏松基因治疗、破骨细胞和成骨细胞的相互作用机制等研究提供理想的动物模型和新型研究手段，具有重要的理论意义和应用价值。
应用领域：骨质疏松症

验证数据

该小鼠具有以下表型：

  • X-Ray放射检测Opg基因纯合缺失小鼠发生骨质疏松 

  • 组织形态学分析证实OPG基因纯合缺失小鼠骨量明显减少：松质骨骨小梁数目减少，连接性降低，间距增大；皮质骨变薄，骨陷窝增多。   

  • Opg敲除小鼠TRAP检测证实纯合子小鼠破骨细胞（OC）明显增多。

  • Opg敲除小鼠在主动脉出现动脉钙化，其特点是没有动脉粥样斑块形成，只是出现动脉中膜钙化。


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Fig1. Opg gene targeting strategy. (a)Schematic representation of gene targeting at the Opg locus. (b)Southern blot analysis by using ES cell genomic DNA digested with EcoRV. +/+:wildtype ES clone; +/-:Positive targeted clone. (c) Genotyping of Opg knockout mice by PCR. (d) RT-PCR and (e) Western blot analysis of RNA and protein from liver of wildtype(+/+),heterozygous(+/-) and homozygous (-/-) Opg knockout mice. The absence of Opg expression in Opg-/- mice was confirmed at both mRNA and protein levels.


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Fig2. Opg-/- mice exhibit osteoporosis and aortic calcification.  (a,b) Radiographs of 2-month-old mice show decreased bone mineral density of leg, pelvis and vertebrae in Opg-/- mice compared with wildtype. (c,d)Opg-/- mice exhibit medial calcification (arrow) aortic calcification (H&E stained, 40x)


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Fig3. High bone turnover in Opg-/- mice.  (a,b)TRAP staining of femoral cortical shaft of wt and Opg-/- mice. Yellow arrowheads indicate TRAP positive osteoblasts. (c,d) Arrows indicate osteoblasts along the bone surface (H&E stained, 40x). Osteoblasts of Opg-/- mice appear more cuboidal in shape than those of wt mice.


References

  1. Xu Yong,et al. High-bone-turnover Osteoporosis and Aortic Calcification in Opg Knockout Mice. Progess in Biochemistry and Biophysics. (2007)34(3):260-266.

  2. Meizhu Yan,et al.Raloxifene inhibits bone loss and improves bone strength through an Opg-independent mechanism.Endocr (2010) 37:55–61.

  3. 李西华, 颜美珠, 许勇, 庞晓芬, 王铸钢。骨保护素基因敲除对小鼠左心室收缩功能的影响。<<上海交通大学学报（医学版）>>2008，28（3）： 

  4. 程少丹, 王拥军, 唐德志, 周泉, 李晨光, 周重建, 施杞。 OPG基因敲除小鼠骨质疏松情况的研究。 <<中国骨质疏松杂志>>2008，14（1）：16－19

  5. 颜美珠，庞小芬，许勇，李西华，孔辉等。雷洛昔芬对骨保护蛋白基因缺失小鼠的抗骨质疏松作用。中华内分泌代谢杂志 2008，24（4） 

发表文献 7篇

1. Osteoprotegerin promotes intimal hyperplasia and contributes to in-stent restenosis: Role of an αVβ3/FAK dependent YAP pathway
发表年份：2020 来源杂志：JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

2. Osteoprotegerin Promotes Liver Steatosis by Targeting the ERK–PPAR-γ–CD36 Pathway
发表年份：2019 来源杂志：DIABETES

3. MicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification
发表年份：2017 来源杂志：PLoS One

4. Role of Osteoprotegerin (OPG) in Bone Marrow Adipogenesis
发表年份：2016 来源杂志：CELLULAR PHYSIOLOGY AND BIOCHEMISTRY

5. Osteoprotegerin-Knockout Mice Developed Early Onset Root Resorption
发表年份：2016 来源杂志：JOURNAL OF ENDODONTICS

6. Osteoprotegerin deficiency leads to deformation of the articular cartilage in femoral head
发表年份：2016 来源杂志：JOURNAL OF MOLECULAR HISTOLOGY

7. Osteoprotegerin deficiency attenuates strontium-mediated inhibition of osteoclastogenesis and bone resorption
发表年份：2011 来源杂志：JOURNAL OF BONE AND MINERAL RESEARCH

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