The protein encoded by the classic MBP gene is a major constituent of the myelin sheath of oligodendrocytes and Schwann cells in the nervous system. However, MBP-related transcripts are also present in the bone marrow and the immune system. These mRNAs arise from the long MBP gene (otherwise called "Golli-MBP") that contains 3 additional exons located upstream of the classic MBP exons. Alternative splicing from the Golli and the MBP transcription start sites gives rise to 2 sets of MBP-related transcripts and gene products. The Golli mRNAs contain 3 exons unique to Golli-MBP, spliced in-frame to 1 or more MBP exons. They encode hybrid proteins that have N-terminal Golli aa sequence linked to MBP aa sequence. The second family of transcripts contain only MBP exons and produce the well-characterized myelin basic proteins. This complex gene structure is conserved among species, suggesting that the MBP transcription unit is an integral part of the Golli transcription unit and that this arrangement is important for the function and/or regulation of these genes.
Interest in MBP has centered on its role in demyelinating diseases, in particular, multiple sclerosis (MS). The target antigen of the autoimmune response in MS has not yet been identified. However, several studies have shown a role for antibodies against MBP in the pathogenesis of MS. Some studies have linked a genetic predisposition to MS to the MBP gene, though a majority have not.
A "molecular mimicry" hypothesis of multiple sclerosis has been suggested, in which T cells are, in essence, confusing MBP with human herpesvirus-6. Researchers in the United States created a synthetic peptide with a sequence identical to that of an HHV-6 peptide. Elevated levels of MBP can be found in the cerebrospinal fluid of patients with HIV infections with signs of encephalopathy, even it is suggested that it is rather an indicator of prognosis for the course of the disease.
It is able to show that T cells were activated by this peptide. These activated T cells also recognized and initiated an immune response against a synthetically created peptide sequence that is identical to part of human MBP. During their research, they found that the levels of these cross-reactive T cells are significantly elevated in multiple sclerosis patients.
Some research has shown that inoculating an animal with MBP to generate an MBP-specific immune response against it increases blood–brain barrier permeability. Permeability is enhanced when the animal is inoculated against non-specific proteins.
A targeted immune response to MBP has been implicated in lethal rabies infection. The inoculation of MBP generates increases the permeability of the blood–brain barrier (BBB), allowing immune cells to enter the brain, the primary site of rabies virus replication. In a study of mice infected with Silver-haired bat rabies virus (SHBRV), the mortality rate of mice treated with MBP improved 20%-30% over the untreated control group. It is significant to note that healthy uninfected mice treated with MBP showed an increase in mortality rate between 0% and 40%.
^Sakamoto Y, Kitamura K, Yoshimura K, Nishijima T, Uyemura K (March 1987). "Complete amino acid sequence of PO protein in bovine peripheral nerve myelin". The Journal of Biological Chemistry. 262 (9): 4208–14. PMID2435734.
^Inouye H, Kirschner DA (January 1991). "Folding and function of the myelin proteins from primary sequence data". Journal of Neuroscience Research. 28 (1): 1–17. doi:10.1002/jnr.490280102. PMID1710279.
^Eylar EH, Brostoff S, Hashim G, Caccam J, Burnett P (September 1971). "Basic A1 protein of the myelin membrane. The complete amino acid sequence". The Journal of Biological Chemistry. 246 (18): 5770–84. PMID5096093.
^Saxe DF, Takahashi N, Hood L, Simon MI (1985). "Localization of the human myelin basic protein gene (MBP) to region 18q22----qter by in situ hybridization". Cytogenetics and Cell Genetics. 39 (4): 246–9. doi:10.1159/000132152. PMID2414074.
^Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID19067971.
^Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M (July 2003). "Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event". The New England Journal of Medicine. 349 (2): 139–45. doi:10.1056/NEJMoa022328. PMID12853586.
^Tejada-Simon MV, Zang YC, Hong J, Rivera VM, Zhang JZ (February 2003). "Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis". Annals of Neurology. 53 (2): 189–97. doi:10.1002/ana.10425. PMID12557285.
^Wood DD, Vella GJ, Moscarello MA (October 1984). "Interaction between human myelin basic protein and lipophilin". Neurochemical Research. 9 (10): 1523–31. doi:10.1007/BF00964678. PMID6083474.
^Edwards AM, Ross NW, Ulmer JB, Braun PE (January 1989). "Interaction of myelin basic protein and proteolipid protein". Journal of Neuroscience Research. 22 (1): 97–102. doi:10.1002/jnr.490220113. PMID2467009.
^Harauz G, Ishiyama N, Hill CM, Bates IR, Libich DS, Farès C (2004). "Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis". Micron. 35 (7): 503–42. doi:10.1016/j.micron.2004.04.005. PMID15219899.
Boylan KB, Ayres TM, Popko B, Takahashi N, Hood LE, Prusiner SB (January 1990). "Repetitive DNA (TGGA)n 5' to the human myelin basic protein gene: a new form of oligonucleotide repetitive sequence showing length polymorphism". Genomics. 6 (1): 16–22. doi:10.1016/0888-7543(90)90443-X. PMID1689270.
Kishimoto A, Nishiyama K, Nakanishi H, Uratsuji Y, Nomura H, Takeyama Y, Nishizuka Y (October 1985). "Studies on the phosphorylation of myelin basic protein by protein kinase C and adenosine 3':5'-monophosphate-dependent protein kinase". The Journal of Biological Chemistry. 260 (23): 12492–9. PMID2413024.
Saxe DF, Takahashi N, Hood L, Simon MI (1985). "Localization of the human myelin basic protein gene (MBP) to region 18q22----qter by in situ hybridization". Cytogenetics and Cell Genetics. 39 (4): 246–9. doi:10.1159/000132152. PMID2414074.
Scoble HA, Whitaker JN, Biemann K (August 1986). "Analysis of the primary sequence of human myelin basic protein peptides 1-44 and 90-170 by fast atom bombardment mass spectrometry". Journal of Neurochemistry. 47 (2): 614–6. doi:10.1111/j.1471-4159.1986.tb04544.x. PMID2426402.
Roth HJ, Kronquist K, Pretorius PJ, Crandall BF, Campagnoni AT (1986). "Isolation and characterization of a cDNA coding for a novel human 17.3K myelin basic protein (MBP) variant". Journal of Neuroscience Research. 16 (1): 227–38. doi:10.1002/jnr.490160120. PMID2427738.
Popko B, Puckett C, Lai E, Shine HD, Readhead C, Takahashi N, Hunt SW, Sidman RL, Hood L (February 1987). "Myelin deficient mice: expression of myelin basic protein and generation of mice with varying levels of myelin". Cell. 48 (4): 713–21. doi:10.1016/0092-8674(87)90249-2. PMID2434243.
Roth HJ, Kronquist KE, Kerlero de Rosbo N, Crandall BF, Campagnoni AT (1987). "Evidence for the expression of four myelin basic protein variants in the developing human spinal cord through cDNA cloning". Journal of Neuroscience Research. 17 (4): 321–8. doi:10.1002/jnr.490170402. PMID2442403.
Shoji S, Ohnishi J, Funakoshi T, Fukunaga K, Miyamoto E, Ueki H, Kubota Y (November 1987). "Phosphorylation sites of bovine brain myelin basic protein phosphorylated with Ca2+-calmodulin-dependent protein kinase from rat brain". Journal of Biochemistry. 102 (5): 1113–20. doi:10.1093/oxfordjournals.jbchem.a122149. PMID2449425.
Wood DD, Moscarello MA (March 1989). "The isolation, characterization, and lipid-aggregating properties of a citrulline containing myelin basic protein". The Journal of Biological Chemistry. 264 (9): 5121–7. PMID2466844.
Edwards AM, Ross NW, Ulmer JB, Braun PE (January 1989). "Interaction of myelin basic protein and proteolipid protein". Journal of Neuroscience Research. 22 (1): 97–102. doi:10.1002/jnr.490220113. PMID2467009.
Streicher R, Stoffel W (May 1989). "The organization of the human myelin basic protein gene. Comparison with the mouse gene". Biological Chemistry Hoppe-Seyler. 370 (5): 503–10. doi:10.1515/bchm3.1989.370.1.503. PMID2472816.
Lennon VA, Wilks AV, Carnegie PR (November 1970). "Immunologic properties of the main encephalitogenic peptide from the basic protein of human myelin". Journal of Immunology. 105 (5): 1223–30. PMID4099924.
Wood DD, Vella GJ, Moscarello MA (October 1984). "Interaction between human myelin basic protein and lipophilin". Neurochemical Research. 9 (10): 1523–31. doi:10.1007/BF00964678. PMID6083474.
Gibson BW, Gilliom RD, Whitaker JN, Biemann K (April 1984). "Amino acid sequence of human myelin basic protein peptide 45-89 as determined by mass spectrometry". The Journal of Biological Chemistry. 259 (8): 5028–31. PMID6201481.