Sackler Faculty of Medicine, Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel.
Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem, Israel.
J Cell Physiol. 2018 Jan;233(1):371-377. doi: 10.1002/jcp.25895. Epub 2017 Jun 5.
The inbred mouse strain C57BL/6 is commonly used for the generation of transgenic mouse and is a well established strain in bone research. Different vendors supply different substrains of C57BL/6J as wild-type animals when genetic drift did not incur any noticeable phenotype. However, we sporadically observed drastic differences in the bone phenotype of "WT" C57BL/6J mice originating from different labs and speculated that these variations are attributable, at least in part, to the variation between C57BL/6J substrains, which is often overlooked. C57BL/6J-OlaHsd is a commonly used substrain that despite a well defined deletion in the alpha-synuclein (Snca) and multimerin-1 (Mmrn1) genes, was reported to display no obvious phenotype and is used as WT control. Here, we compared the bone phenotype of C57BL/6J-OlaHsd (6J-OLA) to C57BL/6J-RccHsd (6J-RCC) and to the original C57BL/6J (6J-JAX). Using μCT analysis, we found that 6J-OLA mice display a significantly lower trabecular bone mass compared to 6J-RCC and 6J-JAX. PCR analysis revealed that both the Snca and Mmrn1 genes are expressed in bone tissue of 6J-RCC animals but not of 6J-OLA mutants, suggesting either one or both genes play a role in bone metabolism. In vitro analysis demonstrated increase in osteoclasts number and decreased osteoblast mineralization in cells derived from 6J-OLA compared with 6J-RCC. Our data may shed light on unexplained differences in basal bone measurements between different research centers and reiterate the importance of specifying the exact substrain type. In addition, our findings describe the physiological role for Mmrn1 and/or Snca in bone remodeling.
近交系小鼠 C57BL/6 常用于转基因小鼠的生成，是骨研究中一种成熟的品系。不同的供应商提供不同的 C57BL/6J 亚系作为野生型动物，因为遗传漂变没有引起任何明显的表型。然而，我们偶尔会观察到来自不同实验室的“WT”C57BL/6J 小鼠的骨表型存在明显差异，并推测这些差异至少部分归因于 C57BL/6J 亚系之间的差异，而这种差异往往被忽视。C57BL/6J-OlaHsd 是一种常用的亚系，尽管在α-突触核蛋白（Snca）和多聚蛋白-1（Mmrn1）基因中有明确的缺失，但据报道没有明显的表型，并被用作 WT 对照。在这里，我们比较了 C57BL/6J-OlaHsd（6J-OLA）与 C57BL/6J-RccHsd（6J-RCC）和原始 C57BL/6J（6J-JAX）的骨表型。使用μCT 分析，我们发现 6J-OLA 小鼠的小梁骨量明显低于 6J-RCC 和 6J-JAX。PCR 分析显示，Snca 和 Mmrn1 基因在 6J-RCC 动物的骨组织中均有表达，但在 6J-OLA 突变体中没有表达，这表明一个或两个基因都可能在骨代谢中发挥作用。体外分析表明，与 6J-RCC 相比，6J-OLA 细胞来源的破骨细胞数量增加，成骨细胞矿化减少。我们的数据可能阐明了不同研究中心之间基础骨测量值存在差异的原因，并再次强调了指定确切亚系类型的重要性。此外，我们的研究结果描述了 Mmrn1 和/或 Snca 在骨重塑中的生理作用。
