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Transferrin in the central nervous system of the shiverer mouse myelin mutant
J R Connor1, A J Roskams, S L Menzies
1Department of Neuroscience and Anatomy, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Abstract:
Transferrin, the iron mobilization protein, and its mRNA are normally present in oligodendrocytes. Previous reports using myelin mutants have shown both a decrease in transferrin protein and mRNA when the oligodendrocyte 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 myelin was used. This animal model was chosen to address the question whether expression of the transferrin message and/or protein correlated more closely to the number of oligodendrocytes (normal) or the amount of myelin (abnormally low). A 1/2 to 2/3 decrease in transferrin protein 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 oligodendrocytes is a requirement for normal expression of transferrin mRNA in brain but is not sufficient for normal values of the protein. The level of Tf protein correlates more closely with the amount of myelin present than it does with the numbers of oligodendrocytes present. These data are consistent with previous reports from our laboratory that transferrin accumulation by oligodendrocytes is associated with myelin production by these cells. These data further suggest transferrin mRNA may be constitutively expressed by oligodendrocytes and that the protein expression is regulated at the level of translation.
Insights
Transferrin protein levels, crucial for iron transport, decrease with reduced myelin in shiverer mice, suggesting a link between myelin production and transferrin accumulation in oligodendrocytes.
Area of Science:
- Neuroscience
- Molecular Biology
- Iron Metabolism
Background:
- Transferrin (Tf) and its mRNA are typically found in oligodendrocytes.
- Previous studies linked decreased Tf and mRNA to compromised oligodendrocyte populations.
Purpose of the Study:
- To investigate if Tf expression correlates with oligodendrocyte number or myelin amount.
- Utilized the shiverer mouse mutant with normal oligodendrocyte numbers but abnormal myelin.
Main Methods:
- Compared Tf protein and mRNA levels in shiverer mice to controls.
- Examined various brain regions and the spinal cord.
Main Results:
- Transferrin protein decreased significantly (1/2 to 2/3) in most brain regions of shiverer mice.
- Transferrin transcript levels in the brain remained unaffected by the shiverer mutation.
- Oligodendrocyte presence is necessary but not sufficient for normal Tf mRNA levels.
Conclusions:
- Transferrin protein levels correlate more closely with myelin amount than oligodendrocyte numbers.
- Oligodendrocyte transferrin accumulation is associated with myelin production.
- Tf mRNA may be constitutively expressed, with protein regulation at the translational level.