We analyzed the location and abundance of transcripts for the 4 CNS myelin protein genes, myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and 2',3'-cyclic nucleotide phosphohydrolase (CNP), in the mouse cervical spinal cord from the time of rapid myelination until adulthood (8-45 d). In the white matter, maximal levels of transcripts were found for e...

Systemic administration of antigen/peptide for peripheral T cell tolerance has long been investigated as a potential approach to therapy of autoimmune diseases. The multiple antimyelin T cell reactivities likely to be associated with multiple sclerosis (MS) impose major difficulties in devising such an immune-specific therapeutic approach to the disease, because targeting T cells specific for a...

To date, very few Ag-based regimens have been defined that could expand T regulatory (Treg) cells to reverse autoimmunity. Additional understanding of Treg function with respect to specificity and broad suppression should help overcome these limitations. Ig-proteolipid protein (PLP)1, an Ig carrying a PLP1 peptide corresponding to amino acid residues 139-151 of PLP, displayed potent tolerogenic...

Proteolipid protein (PLP), the major integral membrane protein of central nervous system myelin, contains 14 cysteine residues within its 276-residue polypeptide chain. We determined the state of all cysteine residues and localized four of them as free thiols a t positions 24, 32, 34, and 168. Four cysteines are connected by disulfide bonds: Cys200-Cys219 and Cys183-Cys227. The remaining six cy...

We have previously shown that patients with multiple sclerosis (MS) have increased T cell responses to the immunodominant region (residues 184-209) of myelin proteolipid protein (PLP). The present study investigated whether this reactivity fluctuates over time and correlates with disease activity. We performed monthly limiting dilution assays for 12-16 mo in four healthy subjects and five patie...

Alternative splicing of the qkI transcript generates multiple isoforms of the selective RNA-binding protein QKI, which play key roles in controlling the homeostasis of their mRNA targets. QKI deficiency in oligodendrocytes of homozygous quakingviable (qk /qk ) mutant mice results in severe hypomyelination, indicating the essential function of QKI in myelinogenesis. However, the molecular mechan...

B-cell CLL/lymphoma 11B (Bcl11b) - a C2H2 zinc finger transcriptional factor - is known to regulate neuronal differentiation and function in the development of the central nervous system (CNS). Although its expression is reduced during oligodendrocyte (OLG) differentiation, its biological role in OLGs remains unknown. In this study, we found that the downregulation of Bcl11b gene expression in ...

To explore the function of genes expressed by myelinating cells we have developed a model system that allows for the inducible ablation of predetermined genes in oligodendrocytes and Schwann cells. The Cre/ loxP recombination system provides the opportunity to generate tissue-specific somatic mutations in mice. We have used a fusion protein between the Cre recombinase and a mutated ligand-bindi...

Wrapping and compaction of myelin sheaths around axons require specific membrane and membrane-associated proteins. Transmembrane proteins like proteolipid protein (PLP), the peripheral myelin protein 22 (PMP-22) and P0 as well as myelin basic protein (MBP) are crucial for this process. We have isolated a rat cDNA, initially denominated NS 3, that is mainly expressed in the myelinating cells of ...