The C57BL/6J mouse exhibits sporadic congenital portosystemic shunts.
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.
Laboratory for Functional and Metabolic Imaging (LIFMET), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. cristina.cudalbu@epfl.ch
Cristina
C
Cudalbu
Valérie A
VA
McLin
Hongxia
H
Lei
Joao M N
JM
Duarte
Anne-Laure
AL
Rougemont
Graziano
G
Oldani
Sylvain
S
Terraz
Christian
C
Toso
Rolf
R
Gruetter
D000792:Angiography; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005973:Glutamine / Q000378:metabolism; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D011170:Portasystemic Shunt, Surgical
D005973:Glutamine