Myelin regulatory factor is encoded by theMyrf/GM98 gene in mice and by theMYRF gene in humans.[5] The family of MyRF-like-proteins also contains the orthologues pqn-47 fromC. elegans and MYRFA fromDictyostelium.[6] All orthologs have aDNA-binding domain of high homology to theSaccharomyces cerevisiae proteinNdt80 (ap53-liketranscription factor) and therefore likely act as a transcription factor.
MyRF is atranscription factor that promotes the expression of many genes important in the production ofmyelin.[7] It is therefore of critical importance in the development and maintenance of myelin sheaths.[8]
The expression of MYRF is specific to mature, myelinatingoligodendrocytes in theCNS.[9][10] It has been shown to be critical for the maintenance of myelin by these cells. Followingablation of MYRF the expression of myelin genes such asPLP1,MBP,MAG andMOG drops rapidly.[8] Therefore, MYRF is a key regulator and likely a direct activator of the expression of these genes.[7]
Mice that lose MYRF during adulthood present with a severe demyelination similar to that seen in animal models ofmultiple sclerosis. This underlines the importance of an active renewal of proteins in themyelin sheath. Further, the activity of MYRF increases during remyelination, suggesting it has a critical role in this process.[8] Animals with repressed Myrf in a proportion ofoligodendrocyte precursor cells showed a delayed functional recovery from spinal cord injury.[11]
Myrf has been shown to be significantly downregulated in a mouse model carrying the same mutation in theNPC1 protein that is underlyingNiemann-Pick type C1 disease, a neurodegenerative process in which dysmyelination is a main pathogenic factor. Therefore, a disruption of oligodendrocyte formation and myelination may be the root cause of the neurological abnormalities.[12]
^Yan X, Lukas J, Witt M, Wree A, Hübner R, Frech M, Köhling R, Rolfs A, Luo J (December 2011). "Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse".Metab Brain Dis.26 (4):299–306.doi:10.1007/s11011-011-9263-9.PMID21938520.S2CID26878522.
