Laboratory for Functional and Metabolic Imaging (LIFMET), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
PLoS One. 2013 Jul 23;8(7):e69782. doi: 10.1371/journal.pone.0069782. Print 2013.
C57BL/6 mice are the most widely used strain of laboratory mice. Using in vivo proton Magnetic Resonance Spectroscopy ((1)H MRS), we have repeatedly observed an abnormal neurochemical profile in the brains of both wild-type and genetically modified mice derived from the C57BL/6J strain, consisting of a several fold increase in cerebral glutamine and two fold decrease in myo-inositol. This strikingly abnormal neurochemical "phenotype" resembles that observed in chronic liver disease or portosystemic shunting and appeared to be independent of transgene, origin or chow and was not associated with liver failure. As many as 25% of animals displayed the abnormal neurochemical profile, questioning the reliability of this model for neurobiology. We conducted an independent study to determine if this neurochemical profile was associated with portosystemic shunting. Our results showed that 100% of the mice with high brain glutamine displayed portosystemic shunting by concomitant portal angiography while all mice with normal brain glutamine did not. Since portosystemic shunting is known to cause alterations in gene expression in many organs including the brain, we conclude that portosystemic shunting may be the most significant problem associated with C57BL/6J inbreeding both for its effect on the central nervous system and for its systemic repercussions.
C57BL/6 小鼠是最广泛使用的实验小鼠品系。通过体内质子磁共振波谱((1)H MRS)，我们反复观察到源自 C57BL/6J 品系的野生型和基因修饰小鼠的大脑中存在异常的神经化学特征，表现为脑谷氨酸显著增加几倍，肌醇降低两倍。这种明显异常的神经化学“表型”类似于慢性肝病或门体分流中观察到的表型，似乎与转基因、起源或饮食无关，也与肝功能衰竭无关。多达 25%的动物表现出异常的神经化学特征，这使得该模型在神经生物学中的可靠性受到质疑。我们进行了一项独立研究，以确定这种神经化学特征是否与门体分流有关。我们的结果表明，大脑谷氨酸水平高的小鼠中，100%存在门体分流，同时伴有门静脉造影；而大脑谷氨酸水平正常的小鼠中，没有门体分流。由于门体分流已知会导致包括大脑在内的许多器官中的基因表达改变，我们得出结论，门体分流可能是与 C57BL/6J 近交系相关的最显著问题，无论是对中枢神经系统还是对全身系统都有影响。
