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HGNC Approved Gene Symbol: MBP
Cytogenetic location: 18q23 Genomic coordinates (GRCh38): 18:76,978,833-77,133,708 (from NCBI)
MBP is a peripheral membrane protein required for maintenance of the compact multilamellar membrane structure of mature myelin. MBP is expressed by oligodendrocytes in central nervous system and Schwann cells in peripheral nervous system (summary by Haas et al., 1995).
Eylar et al. (1971) determined the complete amino acid sequence of MBP. Kamholz et al. (1986) isolated cDNA clones encoding 3 separate forms of MBP: 21.5, 18.5, and 17.2 kD. The 3 forms apparently arise by alternative splicing of a primary MBP transcript. They share a common sequence but differ by the inclusion of a 26-residue amino acid sequence near the N-terminus of the 21.5-kD protein or the absence of an 11-residue AA sequence near the C-terminus of the 17.2-kD protein. The sequences either added to or deleted from the 18.5 kD MBP correspond exactly to mouse exons 2 and 5. The conservation suggests an important role of this sequence in myelination. (The so-called myelin membrane encephalitogenic protein (Dayhoff, 1972) represents the '18.5-kD' form of MBP, as indicated by the amino acid sequence data for MBP (Martenson, 1984).)
By Northern blot analysis of adult mouse tissues, Haas et al. (1995) detected Mbp expression in brain only. Mbp expression in brain was first detected at postnatal day 7, peaked at day 18, and decreased to a lower level in adult mouse.
MBP-related transcripts are present not only in the nervous system, but also in bone marrow and the immune system. These mRNAs are transcribed from a region of 3 exons, located upstream of the classic MBP exons, and belong to the long MBP gene otherwise called 'Golli-MBP.' The most abundant of these mRNAs, called hemopoietic MBP (HMBP), encompasses the sequence encoded by the region zero-prime plus exon 1 and part of intron 1 of the classic MBP gene. Marty et al. (2002) demonstrated that HMBP proteins are present in more than 95% of thymic T cells, which express the corresponding transcripts, as do mature T cells from lymph nodes and spleen. HMBP mRNAs and proteins are also manifest in the majority of spleen B lymphocytes and in B-cell lines. In addition to lymphoid cells, HMBP proteins are in all types of myeloid lineage cells, i.e., macrophages, dendritic cells, and granulocytes, as well as megakaryocytes and erythroblasts. HMBP proteins are also present in CD34(+) bone marrow cells. Furthermore, in highly proliferative cultures, these CD34(+) cells express HMBP RNAs and proteins. Thus, MBP gene products are present both in the nervous system and in the entire hemopoietic system.
By in situ hybridization, Saxe et al. (1985) localized the human myelin basic protein gene to 18q22-qter. Sparkes et al. (1987) confirmed the assignment by means of somatic cell hybridization and in situ hybridization. By a combination of Southern hybridization to a panel of somatic cell hybrid DNAs and in situ hybridization to metaphase chromosomes, Kamholz et al. (1987) mapped the MBP locus to 18q22-q23. They also identified RFLPs associated with the locus. Boylan et al. (1987) found a RFLP in the region of DNA 5-prime to MBP. In 40 subjects studied, heterozygosity was 37%. This should be a useful marker for the MBP gene and for MBP-linked loci on chromosome 18.
Gross (2021) mapped the MBP gene to chromosome 18q23 based on an alignment of the MBP sequence (GenBank BC065248) with the genomic sequence (GRCh38).
Haas et al. (1995) found that mouse Myef2 (619395) bound to the noncoding strand of the proximal MB1 element of the Mbp promoter. In cotransfection assays, Myef2 suppressed expression of the Mbp promoter in mouse fibroblasts, human glioblastoma cells, and rat schwannoma cells.
Associations Pending Confirmation
See 126200 for evidence, based on linkage studies, suggesting that genetic susceptibility to multiple sclerosis is associated in some way with the MBP gene.
The 'shiverer' (shi) neurologic mutation in the mouse is located in the MBP gene of that species (Sidman, 1983; Sidman et al., 1985). Shiverer mutant mice carry a deletion of a major portion of their MBP sequence (Roach et al., 1983). The shi locus is on mouse chromosome 18, an interesting numerical coincidence. (Peptidase A, 169800, called Pep-1 in the mouse, is also on chromosome 18 of both species (Lalley and McKusick, 1985).) Readhead et al. (1987) introduced the wildtype MBP gene into the germline of shiverer mice by microinjection into fertilized eggs. Popko et al. (1987) did similar studies in mice homozygous for the mutation 'myelin deficient' (mld), an allele of shiverer. The mld mouse exhibits decreased CNS myelination, tremors, and convulsions of progressively increasing severity leading to early death. The homozygous shiverer mice in whom the gene for MBP had been injected showed no more neurologic symptoms and survived normally. Correct temporal and spatial expression of the MBP gene was achieved. Four different forms of MBP produced by alternative RNA splicing were found. Increasing myelination and decrease in tremors and convulsions were observed in treated mld mice. Whereas shiverer mice completely lack MBP, myelin deficient mice have a reduced amount. Molineaux et al. (1986) showed that the MBP gene has undergone a major rearrangement in the shiverer mutation, namely, deletion of a 20-kb region. The 5-prime breakpoint is in the second intron and the 3-prime breakpoint is located 2 kb beyond the last MBP exon.
As a model for the detection of human genetic disease in preimplantation embryos, Gomez et al. (1990) described a method in which trophectoderm biopsy samples from viable mouse blastocysts were analyzed for the presence of a normal or mutant (shiverer) allele of the MBP gene by the polymerase chain reaction (PCR). Prenatal diagnosis could be completed in less than 7 hours. Of the recovered blastocysts, 96% survived biopsy, as judged by re-formation of a blastocyst cavity in culture. Of the biopsied embryos, 59% established pregnancy by day 6.5, compared to 88% of unmanipulated controls.
Boylan, K. B., Takahashi, N., Diamond, M., Hood, L. E., Prusiner, S. B. DNA length polymorphism located 5-prime to the human myelin basic protein gene. Am. J. Hum. Genet. 40: 387-400, 1987. [PubMed: 2437796]
Dayhoff, M. O. Atlas of Protein Sequence and Structure. Myelin membrane encephalitogenic protein. Vol. 5. Washington: National Biomedical Research Foundation (pub.) 1972. P. D324.
Eylar, E. H., Brostoff, S., Hashim, G., Westall, F. C. Basic A1 protein of the myelin membrane: the complete amino acid sequence. J. Biol. Chem. 246: 5770-5784, 1971. [PubMed: 5096093]
Gomez, C. M., Muggleton-Harris, A. L., Whittingham, D. G., Hood, L. E., Readhead, C. Rapid preimplantation detection of mutant (shiverer) and normal alleles of the mouse myelin basic protein gene allowing selective implantation and birth of live young. Proc. Nat. Acad. Sci. 87: 4481-4484, 1990. [PubMed: 1693773] [Full Text: https://doi.org/10.1073/pnas.87.12.4481]
Gross, M. B. Personal Communication. Baltimore, Md. 6/22/2021.
Haas, S., Steplewski, A., Siracusa, L. D., Amini, S., Khalili, K. Identification of a sequence-specific single-stranded DNA binding protein that suppresses transcription of the mouse myelin basic protein gene. J. Biol. Chem. 270: 12503-12510, 1995. [PubMed: 7539003] [Full Text: https://doi.org/10.1074/jbc.270.21.12503]
Kamholz, J., de Ferra, F., Puckett, C., Lazzarini, R. Identification of three forms of human myelin basic protein by cDNA cloning. Proc. Nat. Acad. Sci. 83: 4962-4966, 1986. [PubMed: 2425357] [Full Text: https://doi.org/10.1073/pnas.83.13.4962]
Kamholz, J., Spielman, R., Gogolin, K., Modi, W., O'Brien, S., Lazzarini, R. The human myelin-basic-protein gene: chromosomal localization and RFLP analysis. Am. J. Hum. Genet. 40: 365-373, 1987. [PubMed: 2437795]
Lalley, P. A., McKusick, V. A. Report of the committee on comparative mapping (HGM8). Cytogenet. Cell Genet. 40: 536-566, 1985. [PubMed: 3933918] [Full Text: https://doi.org/10.1159/000132187]
Martenson, R. E. Myelin basic protein speciation. Prog. Clin. Biol. Res. 146: 511-521, 1984. [PubMed: 6201921]
Marty, M. C., Alliot, F., Rutin, J., Fritz, R., Trisler, D., Pessac, B. The myelin basic protein gene is expressed in differentiated blood cell lineages and in hemopoietic progenitors. Proc. Nat. Acad. Sci. 99: 8856-8861, 2002. [PubMed: 12084930] [Full Text: https://doi.org/10.1073/pnas.122079599]
Molineaux, S. M., Engh, H., de Ferra, F., Hudson, L., Lazzarini, R. A. Recombination within the myelin basic protein gene created the dysmyelinating shiverer mouse mutation. Proc. Nat. Acad. Sci. 83: 7542-7546, 1986. [PubMed: 2429310] [Full Text: https://doi.org/10.1073/pnas.83.19.7542]
Popko, B., Puckett, C., Lai, E., Shine, H. D., Readhead, C., Takahashi, N., Hunt, S. W., III, Sidman, R. L., Hood, L. Myelin deficient mice: expression of myelin basic protein and generation of mice with varying levels of myelin. Cell 48: 713-721, 1987. [PubMed: 2434243] [Full Text: https://doi.org/10.1016/0092-8674(87)90249-2]
Readhead, C., Popko, B., Takahashi, N., Shine, H. D., Saavedra, R. A., Sidman, R. L., Hood, L. Expression of a myelin basic protein gene in transgenic shiverer mice: correction of the dysmyelinating phenotype. Cell 48: 703-712, 1987. [PubMed: 2434242] [Full Text: https://doi.org/10.1016/0092-8674(87)90248-0]
Roach, A., Boylan, K., Horvath, S., Prusiner, S. B., Hood, L. E. Characterization of cloned cDNA representing rat myelin basic protein: absence of expression in shiverer mutant mice. Cell 34: 799-806, 1983. [PubMed: 6194889] [Full Text: https://doi.org/10.1016/0092-8674(83)90536-6]
Roach, A., Takahashi, N., Pravtcheva, D., Ruddle, F., Hood, L. Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 42: 149-155, 1985. [PubMed: 2410137] [Full Text: https://doi.org/10.1016/s0092-8674(85)80110-0]
Saxe, D. F., Takahashi, N., Hood, L., Simon, M. I. Localization of the human myelin basic protein gene (MBP) to region 18q22-qter by in situ hybridization. Cytogenet. Cell Genet. 39: 246-249, 1985. [PubMed: 2414074] [Full Text: https://doi.org/10.1159/000132152]
Sheremata, W., Cosgrove, J. B. R., Hylar, E. H. Cellular hypersensitivity to basic myelin (A1) protein and clinical multiple sclerosis. New Eng. J. Med. 291: 14-17, 1974. [PubMed: 4598923] [Full Text: https://doi.org/10.1056/NEJM197407042910104]
Sidman, R. L., Conover, C. S., Carson, J. H. Shiverer gene maps near the distal end of chromosome 18 in the house mouse. Cytogenet. Cell Genet. 39: 241-245, 1985. [PubMed: 2414073] [Full Text: https://doi.org/10.1159/000132151]
Sidman, R. Personal Communication. Boston, Mass. 1983.
Sparkes, R. S., Mohandas, T., Heinzmann, C., Roth, H. J., Klisak, I., Campagnoni, A. T. Assignment of the myelin basic protein gene to human chromosome 18q22-qter. Hum. Genet. 75: 147-150, 1987. [PubMed: 2434411] [Full Text: https://doi.org/10.1007/BF00591076]
Takahashi, N., Roach, A., Teplow, D. B., Prusiner, S. B., Hood, L. Cloning and characterization of the myelin basic protein gene from mouse: one gene can encode both 14 kd and 18.5 kd MBPs by alternate use of exons. Cell 42: 139-148, 1985. [PubMed: 2410136] [Full Text: https://doi.org/10.1016/s0092-8674(85)80109-4]