| First Author | Jensen NA | Year | 1998 |
| Journal | Oncogene | Volume | 16 |
| Issue | 16 | Pages | 2123-9 |
| PubMed ID | 9572493 | Mgi Jnum | J:47290 |
| Mgi Id | MGI:1203265 | Doi | 10.1038/sj.onc.1201739 |
| Citation | Jensen NA, et al. (1998) Failure of central nervous system myelination in MBP/c-myc transgenic mice: evidence for c-myc cytotoxicity. Oncogene 16(16):2123-9 |
| abstractText | c-myc is a member of the helix-loop-helix/leucine zipper family of proteins that modulate the transcriptional activity of specific target genes. Although aberrant c-myc expression has been reported to play a role in multistage carcinogenesis in astrocytic gliomas, little is known about the effects of the expression of c-myc on oligodendrocytes. Using transgenic animals expressing a human c-myc oncogene under transcriptional control of the myelin basic protein gene, we investigated the effect of overexpression of this oncogene in oligodendrocytes. The MBP/c-myc transgenic mice developed severe neurological disturbances characterized by action tremors and recurrent seizures, and pre-mature death during postnatal weeks three to five. Affected transgenic mice of various strains had severely hypomyelinated central nervous systems and expressed low levels of c-myc, myelin basic protein (MBP) and proteolipid protein (PLP) mRNAs in the brain. These c-myc transgenic mice also exhibited an increased number of TUNEL positive nuclei, which in most cases were located in cells that expressed c-myc, as judged by double immunohistochemistry. There was no evidence of brain tumors in the c-myc transgenic mice, including heterozygous mice from two strains that had normal lifespans. These observations indicate that the myelin deficiency observed in the MBP/c-myc transgenic animals results from a cytotoxic effect of the c-myc transgene. |
