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Publication : Rearrangement and reactivation of the myelin basic protein locus in myelin-deficient (mld) mouse brain.

First Author  Sun Y Year  1997
Journal  J Neurochem Volume  68
Issue  2 Pages  457-68
PubMed ID  9003030 Mgi Jnum  J:37860
Mgi Id  MGI:85256 Doi  10.1046/j.1471-4159.1997.68020457.x
Citation  Sun Y, et al. (1997) Rearrangement and reactivation of the myelin basic protein locus in myelin-deficient (mld) mouse brain. J Neurochem 68(2):457-68
abstractText  Myelin-deficient (mid) is a complex mutation affecting the myelin basic protein (MBP) locus of the mouse. It consists of duplication and partial inversion of the MBP gene and results in a dysfunctional MBP locus. The mutant phenotype is reversed, both in vivo and in vitro, in similar to 5% of mid oligodendrocytes. One possible mechanism for the somatic reversion is recombination between homologous sequences of the duplicated gene copies to reconstitute a functional MBP locus. There are several possible recombination events that could reconstitute a functional MBP locus by DNA rearrangement, Two of these would result in reinversion and circularization of specific MBP gene sequences, respectively. In this work polymerase chain reaction analysis was used to detect both reinverted and circularized MBP gene sequences in mid mouse tissues, indicating that DNA rearrangement at the MBP locus does occur. Analysis of individually harvested cells showed that in revertant MBP-positive mid oligodendrocytes DNA rearrangement at the MBP locus was correlated with reactivation of the MBP gene, Fluctuation analysis showed that reactivation of the MBP locus is a stochastic event occurring with a frequency of similar to 1.4 x 10(-6) per cell per cell cycle during oligodendrocyte development. The frequency of rearrangement and reactivation of the MBP locus was comparable in double mutant (mid/mid, scid/scid) and single mutant (mid/mid, +(scid)/+(scid)) mice, indicating that the scid factor is not required for MBP gene reactivation in mid. The significance of DNA rearrangement in mammalian development is discussed.
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