Transcriptional upregulation of myelin components in spontaneous myelin basic protein-deficient mice

• Published in: Brain research Vol. 1606; pp. 125 - 132
• Main Authors: Staats, Kim A, Pombal, Diana, Schönefeldt, Susann, Van Helleputte, Lawrence, Maurin, Hervé, Dresselaers, Tom, Govaerts, Kristof, Himmelreich, Uwe, Van Leuven, Fred, Van Den Bosch, Ludo, Dooley, James, Humblet-Baron, Stephanie, Liston, Adrian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.05.2015
• Subjects: Animals; Brain - pathology; Connectivity; Knockout; Mice; Mice, Inbred C57BL; Mice, Mutant Strains - genetics; Mice, Mutant Strains - physiology; Motor Activity - genetics; Murine MRI; Mutation; Myelin; Myelin basic protein; Myelin Basic Protein - genetics; Myelin Sheath - genetics; Neurology; Oligodendrocytes; Phenotype; Signal Transduction - genetics; Transcriptional Activation; Up-Regulation; White Matter - pathology; Connectivity; Murine MRI; Myelin; Myelin basic protein; Knockout; Oligodendrocytes
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2015.02.021

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.