Abstract
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.
Highlights
In the last three decades, mouse models have contributed to enormous advances in characterizing the molecular underpinnings of disease through the use of transgenesis and other approaches
The C57BL/6 strain is one of the most widely used for both transgenesis and environmental exposure experiments [1,2,3,4,5]
Since establishing the Centre d’Imagerie BioMedicale (CIBM) (Centre d’Imagerie Biomedicale) in 2005, we have repetitively observed an abnormal neurochemical pattern consisting of increased cerebral glutamine (Gln) concentration and decreased myo-inositol (Ins) concentration in the brains of both wild-type and genetically modified mice, all of which were derived from the C57BL/6J strain
Summary
In the last three decades, mouse models have contributed to enormous advances in characterizing the molecular underpinnings of disease through the use of transgenesis and other approaches. Low tumor incidence is one of its many advantages, unlike the high frequency in early mouse-based experiments Since establishing the CIBM (Centre d’Imagerie Biomedicale) in 2005, we have repetitively observed an abnormal neurochemical pattern consisting of increased cerebral glutamine (Gln) concentration and decreased myo-inositol (Ins) concentration in the brains of both wild-type and genetically modified mice, all of which were derived from the C57BL/6J strain. Gln and Ins were the only substantial changes in the neurochemical profile, consisting of 20 brain metabolites. This neurochemical ‘‘phenotype’’ was reminiscent of what has been described in patients with chronic liver disease [8,9,10]. The findings appeared to have a high incidence and to be independent of transgene, origin, chow, and type of experiment
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