title: Transcriptional upregulation of myelin components in spontaneous myelin basic protein-deficient mice.
abstract: Myelin is essential for efficient signal transduction in the nervous system comprising of multiple proteins. The intricacies of the regulation of the formation of myelin, and its components, are not fully understood. Here, we describe the characterization of a novel myelin basic protein (Mbp) mutant mouse, mbp(jive), which spontaneously occurred in our mouse colony. These mice displayed the onset of a shaking gait before 3 weeks of age and seizure onset before 2 months of age. Due to a progressive increase of seizure intensity, mbp(jive) mice experienced premature lethality at around 3 months of age. Mbp mRNA transcript or protein was undetectable and, accordingly, genetic analysis demonstrated a homozygous loss of exons 3 to 6 of Mbp. Peripheral nerve conductance was mostly unimpaired. Additionally, we observed grave structural changes in white matter predominant structures were detected by T1, T2 and diffusion weighted magnetic resonance imaging. We additionally observed that Mbp-deficiency results in an upregulation of Qkl, Mag and Cnp, suggestive of a regulatory feedback mechanism whereby compensatory increases in Qkl have downstream effects on Mag and Cnp. Further research will clarify the role and specifications of this myelin feedback loop, as well as determine its potential role in therapeutic strategies for demyelinating disorders.
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Staats
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Diana
authors.initials: D
authors.lastname: Pombal
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Susann
authors.initials: S
authors.lastname: Schönefeldt
authors.affiliation: Laboratory of Neurobiology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven, Leuven, Belgium; VIB Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Van Helleputte
authors.affiliation: Experimental Genetics Group LEGTEGG, University of Leuven, Leuven, Belgium.
authors.forename: Hervé
authors.initials: H
authors.lastname: Maurin
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Govaerts
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.affiliation: Experimental Genetics Group LEGTEGG, University of Leuven, Leuven, Belgium.
authors.forename: Fred
authors.initials: F
authors.lastname: Van Leuven
authors.affiliation: Laboratory of Neurobiology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven, Leuven, Belgium; VIB Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. Electronic address: stephanie.humbletbaron@med.kuleuven.be.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Humblet-Baron
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium; Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. Electronic address: adrian.liston@vib.be.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics* / Q000502:physiology*; D009043:Motor Activity / Q000235:genetics; D009154:Mutation; D004676:Myelin Basic Protein / Q000235:genetics*; D009186:Myelin Sheath / Q000235:genetics*; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation; D066127:White Matter / Q000473:pathology
chemical_list: D004676:Myelin Basic Protein
keywords: Connectivity; Knockout; Murine MRI; Myelin; Myelin basic protein; Oligodendrocytes