Decreased body weight in young Osterix-Cre transgenic mice results in delayed cortical bone expansion and accrual
Decreased body weight in young Osterix-Cre transgenic mice results in delayed cortical bone expansion and accrual
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DOI：
10.1007/s11248-011-9581-z
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发表时间：
2012-08-01
影响因子：
3
通讯作者：
Zajac, Jeffrey D.
中科院分区：
文献类型：
--
作者：
Davey, Rachel A.;Clarke, Michele V.;Zajac, Jeffrey D.
使用Cre/loxP系统的条件性基因失活在我们对广泛学科中基因功能的理解方面取得了重大进展。在文献中越来越明显的是，Cre转基因小鼠本身可能具有表型。在接下来的研究中，我们描述了一种常用的研究成骨细胞的Cre转基因小鼠系OSX-GFP：：Cre(OSX-Cre)小鼠的骨表型。用显微断层摄影术(MU CT)测定6周龄和12周龄OSX-CRE小鼠股骨的皮质和骨小梁参数。在6周龄时，与野生型对照组相比，OSX-Cre小鼠体重减轻了22%(P<；0.0001)，皮质骨扩张和增加延迟，特征是骨膜周长减少了7%(P<；0.05)，皮质厚度减少了11%(P<；0.01)。重要的是，骨骼未成熟的OSX-CRE小鼠在6周大时的皮质骨表型可以解释为它们的低体重。OSX-CRE小鼠12周龄时体重增加和皮质发育迟缓，与野生型对照组无差异。总而言之，表达OSX-Cre的小鼠在没有多西环素治疗的情况下表现出延迟的生长表型，表现为6周龄时皮质骨扩张和骨积累减少，这是体重下降的间接结果。虽然这种生长延迟可以在12周大的成年鼠身上克服，但在评估使用OSX-CRE小鼠系产生的骨骼未成熟Cre/loxP基因敲除小鼠的实验数据时，必须谨慎并进行适当的数据分析，以避免误解。
Conditional gene inactivation using the Cre/loxP system has lead to significant advances in our understanding of the function of genes in a wide range of disciplines. It is becoming increasingly apparent in the literature, that Cre transgenic mice may themselves have a phenotype. In the following study we describe the bone phenotype of a commonly used Cre transgenic mouse line to study osteoblasts, the Osx-GFP::Cre (Osx-Cre) mice. Cortical and trabecular bone parameters were determined in the femurs of Osx-Cre mice at 6 and 12 weeks of age by microtomography (mu CT). At 6 weeks of age, Osx-Cre mice had reduced body weight by 22% (P < 0.0001) and delayed cortical bone expansion and accrual, characterized by decreases in periosteal circumference by 7% (P < 0.05) and cortical thickness by 11% (P < 0.01), compared to wild type controls. Importantly, the cortical bone phenotype of the skeletally immature Osx-Cre mice at 6 weeks of age could be accounted for by their low body weight. The delayed weight gain and cortical growth of Osx-Cre mice was overcome by 12 weeks of age, with no differences observed between Osx-Cre and wild type controls. In conclusion, Osx-Cre expressing mice display a delayed growth phenotype in the absence of doxycycline treatment, evidenced by decreased cortical bone expansion and accrual at 6 weeks of age, as an indirect result of decreased body weight. While this delay in growth is overcome by adulthood at 12 weeks of age, caution together with appropriate data analysis must be considered when assessing the experimental data from skeletally immature Cre/loxP knockout mice generated using the Osx-Cre mouse line to avoid misinterpretation.