The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts

PLoS One. 2013 Jul 23;8(7):e69782. doi: 10.1371/journal.pone.0069782. Print 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiography
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Glutamine / metabolism
  • Immunohistochemistry
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred C57BL
  • Portasystemic Shunt, Surgical*

Substances

  • Glutamine

Grants and funding

This study was supported by the Centre d’Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL and the Leenaards and Jeantet Foundations; SNF grant 131087; SNF grant 122498. CT was supported by the Swiss National Science Foundation (SCORE grant 3232230-126233). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.