| First Author | Akowitz A | Year | 1986 |
| Journal | Trans Am Soc Neurochem | Volume | 17 |
| Pages | 108 (Abstr.) | Mgi Jnum | J:15385 |
| Mgi Id | MGI:63508 | Citation | Akowitz A, et al. (1986) A partial duplication of the myelin basic protein gene in MLD mice. Trans Am Soc Neurochem 17:108 (Abstr.) |
| abstractText | Full text of Abstract. 32 A PARTIAL DUPLICATION OF THE MYELIN BASIC PROTEIN GENE IN MLD MICE. Akowitz,*A., Scheld, *K., Barbarese, E., and Carson,* J.H. U. Conn. Health Center, Farmington, CT 06032 The mld mutation is an allele of the shiverer mutation. Both have been mapped to the distal end of chromosome 18 and cause a similar clinical phenotype. The shiverer mutation is a deletion that impinges on the myelin basic protein (MBP) structural gene and affects MBP expression specifically. We have compared the effects of the shiverer and mld mutations on: the level of expression of MBPs by Western blotting, the level of MBP specific mRNA by Northern blotting, and on the structure of the MBP gene by Southern blotting. We have analyzed homozygous and heterozygous shiverer and mld animals as well as shi/mld heterozygotes on four different congenic backgrounds. The results indicate that in homozygous mice both the shiverer and mld mutations cause a severe reduction in the levels of MBP and MBP specific mRNA. This effect is expressed co-dominantly in heterozygous animals in which the levels of MBP and MBP specific mRNA are reduced by approximately half relative to wild type. In shi/mld heterozygotes the levels of MBP and MBP specific mRNA are similar to those found in homozygous mutant mice. Analysis of Southern blots of genomic DNA digested with a variety of restriction enzymes and hybridized with probes representing various portions of the MBP gene indicates that while in the shiverer mutation a portion of the gene is deleted, in the mld mutation a portion of the MBP gene is duplicated. Restriction mapping indicates that the duplicated region in mld is not immediately adjacent to the intact MBP structural gene. However, genetic experiments indicate that they are closely linked. The duplication in mld co-segregates with the mld phenotype and may be responsible for extinguishing expression from the MBP gene. |
