Mobp-KO Mouse

Mobp, short for Myelin-associated Oligodendrocyte Basic Protein, is a relatively abundant CNS-specific myelin protein. It plays a crucial role in stabilizing the myelin sheath in the central nervous system (CNS), which is essential for the rapid saltatory conduction of action potentials within the CNS and for sustaining neuronal health. Its synthesis is regulated by the non-receptor tyrosine kinase Fyn, and it affects the morphological differentiation of oligodendrocytes [3,6].

In multiple system atrophy (MSA), decreased MOBP mRNA levels significantly correlated with increased DNA methylation. MOBP is mislocalized into the glial cytoplasmic inclusions (GCIs) in MSA, where it interacts with α-synuclein, suggesting its relevance to the pathogenesis of MSA [2]. In multiple sclerosis (MS), T-cell autoimmunity against MOBP can be detected, and MOBP-reactive T-cells can be pathogenic in mouse models, indicating it is a relevant primary target autoantigen in MS [3]. In a study on sporadic frontotemporal dementia (sFTD), a candidate locus on chromosome 3 in the intergenic region between RPSA and MOBP was found to contribute to an increased risk for sFTD through effects on expression and/or splicing in the brain cortex [1]. A case-control study in a Greek population found no association between the MOBP rs616147 polymorphism and amyotrophic lateral sclerosis (ALS) [4]. In neonatal mice, Abx-induced gut dysbiosis led to increased expression of myelin-related genes including Mobp in the pre-frontal cortex, and this could be reversed by butyrate [5]. In a mouse model of depression, inhibiting the expression of Mobp blocked ketamine's long-lasting antidepressant effects, suggesting a role of Mobp-dependent myelin repair in ketamine's antidepressant mechanism [7].

In conclusion, Mobp is essential for myelin sheath stability and oligodendrocyte morphological differentiation. Studies using various animal models, especially mouse models, have revealed its significance in neurodegenerative diseases such as MSA, MS, and sFTD, as well as in the antidepressant mechanism of ketamine. These findings contribute to our understanding of the biological functions of Mobp and the underlying mechanisms of related diseases.

References:

1. Manzoni, Claudia, Kia, Demis A, Ferrari, Raffaele, Hardy, John, Escott-Price, Valentina. 2024. Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia. In American journal of human genetics, 111, 1316-1329. doi:10.1016/j.ajhg.2024.05.017. https://pubmed.ncbi.nlm.nih.gov/38889728/

2. Bettencourt, Conceição, Miki, Yasuo, Piras, Ignazio S, Huentelman, Matt J, Holton, Janice L. 2021. MOBP and HIP1 in multiple system atrophy: New α-synuclein partners in glial cytoplasmic inclusions implicated in the disease pathogenesis. In Neuropathology and applied neurobiology, 47, 640-652. doi:10.1111/nan.12688. https://pubmed.ncbi.nlm.nih.gov/33368549/

3. Kaushansky, Nathali, Eisenstein, Miriam, Zilkha-Falb, Rina, Ben-Nun, Avraham. 2009. The myelin-associated oligodendrocytic basic protein (MOBP) as a relevant primary target autoantigen in multiple sclerosis. In Autoimmunity reviews, 9, 233-6. doi:10.1016/j.autrev.2009.08.002. https://pubmed.ncbi.nlm.nih.gov/19683076/

4. Liampas, Ioannis, Siokas, Vasileios, Aloizou, Athina-Maria, Hadjigeorgiou, Georgios M, Dardiotis, Efthimios. 2021. MOBP rs616147 Polymorphism and Risk of Amyotrophic Lateral Sclerosis in a Greek Population: A Case-Control Study. In Medicina (Kaunas, Lithuania), 57, . doi:10.3390/medicina57121337. https://pubmed.ncbi.nlm.nih.gov/34946282/

5. Keogh, Ciara E, Kim, Danielle H J, Pusceddu, Matteo M, Barboza, Mariana, Gareau, Mélanie G. 2020. Myelin as a regulator of development of the microbiota-gut-brain axis. In Brain, behavior, and immunity, 91, 437-450. doi:10.1016/j.bbi.2020.11.001. https://pubmed.ncbi.nlm.nih.gov/33157256/

6. Schäfer, Isabelle, Müller, Christina, Luhmann, Heiko J, White, Robin. 2016. MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes. In Journal of cell science, 129, 930-42. doi:10.1242/jcs.172148. https://pubmed.ncbi.nlm.nih.gov/26801084/

7. Huang, Chaoli, Wu, Zifeng, Wang, Di, Hashimoto, Kenji, Yang, Chun. 2023. Myelin-associated oligodendrocytic basic protein-dependent myelin repair confers the long-lasting antidepressant effect of ketamine. In Molecular psychiatry, 29, 1741-1753. doi:10.1038/s41380-023-02288-5. https://pubmed.ncbi.nlm.nih.gov/37848708/