Opg-KO

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。

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.

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)

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）