The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts.

The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts.
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DOI:
10.1371/journal.pone.0069782
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Gruetter R
Gruetter R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cudalbu C;McLin VA;Lei H;Duarte JM;Rougemont AL;Oldani G;Terraz S;Toso C;Gruetter R

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C57BL/6 小鼠是最广泛使用的实验室小鼠品系。使用体内质子磁共振波谱 (1H MRS),我们反复观察到源自 C57BL/6J 品系的野生型和转基因小鼠大脑中异常的神经化学特征,包括脑谷氨酰胺增加数倍和肌醇减少两倍。这种显着异常的神经化学“表型”类似于在慢性肝病或门体分流中观察到的现象,并且似乎与转基因、起源或食物无关,并且与肝衰竭无关。多达 25% 的动物表现出异常的神经化学特征,质疑该神经生物学模型的可靠性。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相关。我们的结果表明,通过伴随门静脉造影,100% 脑谷氨酰胺高的小鼠表现出门体分流,而所有脑谷氨酰胺正常的小鼠则没有。由于已知门体分流会导致包括大脑在内的许多器官的基因表达改变,因此我们得出结论,门体分流可能是与 C57BL/6J 近交相关的最重要问题,因为它对中枢神经系统的影响及其全身影响。
C57BL/6 mice are the most widely used strain of laboratory mice. Using in vivo proton Magnetic Resonance Spectroscopy (1H 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.
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