TRANSFERRIN IN THE CENTRAL-NERVOUS-SYSTEM OF THE SHIVERER MOUSE MYELIN MUTANT

Transferrin, the iron mobilization protein, and its mRNA are normally present in oligodendrocytes. Previous reports using myelin mutants hav e shown both a decrease in transferrin protein and mRNA when the oligo dendrocyte population is compromised. In this study the shiverer mouse mutant in which the oligodendrocyte population is numerically normal, but has both quantitatively diminished and qualitatively abnormal mye lin was used. This animal model was chosen to address the question whe ther expression of the transferrin message and/or protein correlated m ore closely to the number of oligodendrocytes (normal) or the amount o f myelin (abnormally low). A 1/2 to 2/3 decrease in transferrin protei n occurred in all brain regions examined except for the spinal cord in the shiverer group compared to both heterozygous littermates and wild type controls. Levels of transferrin transcripts in the brain are not affected by the shiverer mutation. These results taken with previous reports from this laboratory indicate that the presence of oligodendro cytes is a requirement for normal expression of transferrin mRNA in br ain but is not sufficient for normal values of the protein. The level of Tf protein correlates more closely with the amount of myelin presen t than it does with the numbers of oligodendrocytes present. These dat a are consistent with previous reports from our laboratory that transf errin accumulation by oligodendrocytes is associated with myelin produ ction by these cells. These data further suggest transferrin mRNA may be constitutively expressed by oligodendrocytes and that the protein e xpression is regulated at the level of translation. (C) 1993 Wiley-Lis s, Inc.