Abstract
C57BL/6J, FVB/N and 129/SvJ mice are commonly used as background strains to engineer genetic models of brain pathologies and psychiatric disorders. Magnetic resonance imaging (MRI) and spectroscopy provide alternative approaches to neuroanatomy, histology and neurohistochemistry for investigating the correlation between genes and brain neuroanatomy and neurometabolism in vivo. We used these techniques to non-invasively characterize the cerebral morphologic and metabolic endophenotypes of inbred mouse strains commonly used in neurological and behavioral research. We observed a great variability in the volume of ventricles and of structures involved in cognitive function (cerebellum and hippocampus) among these strains. In addition, distinct metabolic profiles were evidenced with variable levels of N-acetylaspartate, a neuronal marker, and of choline, a compound found in membranes and myelin. Besides, significant differences in high-energy phosphates and phospholipids were detected. Our findings demonstrate the great morphologic and metabolic heterogeneity among C57BL/6J, FVB/N and 129/SvJ mice. They emphasize the importance of selecting the appropriate genetic background for over-expressing or silencing a gene and provide some directions for modeling symptoms that characterize psychiatric disorders such as autism, schizophrenia and depression.
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Abbreviations
- B6:
-
C57BL/6J
- Cho:
-
Choline
- tCr:
-
total creatine
- FVB:
-
FVB/N
- Glx:
-
glutamate + glutamine
- MRI:
-
magnetic resonance imaging
- MRS:
-
magnetic resonance spectroscopy
- myo-Ins:
-
myo-Inositol
- NAA:
-
N-acetylaspartate
- NAAG:
-
N-acetylaspartylglutamate
- Pi:
-
inorganic phosphate
- PCr:
-
phosphocreatine
- PDE:
-
phosphodiesters
- PME:
-
phosphomonoesters
- TE:
-
time of echo
- 129:
-
129/ SvJ
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Acknowledgments
This work is supported by grants from CNRS (Centre National de la Recherche Scientifique), Programme National Imagerie du Petit Animal (CNRS, CEA), IUF (Institut Universitaire de France) and Action Concertée Incitative “Plates-formes d’explorations fonctionnelles thématisées” (ACI 2003). The authors are grateful to Michèle Carlier for assistance in statistical analysis.
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Penet, MF., Laigle, C., Fur, Y.L. et al. In vivo Characterization of Brain Morphometric and Metabolic Endophenotypes in Three Inbred Strains of Mice Using Magnetic Resonance Techniques. Behav Genet 36, 732–744 (2006). https://doi.org/10.1007/s10519-006-9077-4
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DOI: https://doi.org/10.1007/s10519-006-9077-4