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Published on: February 17, 2016
Abnormal myelinogenesis both in the white and gray matter of the attractin-deficient mv rat
Takeshi Izawa1, Jyoji Yamate, Robin J M Franklin
1Laboratory of Veterinary Pathology, Osaka Prefecture University, Rinku Orai-Kita, Izumisano, Osaka 598-8531, Japan.
Abstract:
The myelin vacuolation (mv) rat exhibits hypomyelination and vacuole formation in the myelin throughout the CNS, caused by a null mutation in the attractin gene. Myelin alterations in the spinal cord of mv rats progress during postnatal development and are more prominent in the white matter. In contrast, microglial activation is confined to the gray matter of mv rats. We here investigate the distribution and expression patterns of major CNS myelin proteins in the spinal cord of mv rats during the development of the myelin lesions. Immunohistochemical and Western blot analyses demonstrated a considerable reduction in the expression of major CNS myelin proteins both in the white and gray matter of mv rats, which was consistent with the morphological alterations of myelin sheaths. Real-time PCR analysis revealed a significant decrease in expression of proteolipid protein (PLP) mRNA both in the white and gray matter of mv rats. However, there was no significant difference between control and mv rats in the cell number of PLP mRNA-positive oligodendrocytes either in the white or gray matter, suggesting an impairment of myelin protein production by oligodendrocytes. Our results indicate that myelinogenesis but not oligodendrogenesis is severely altered both in the white and gray matter of mv rats.
Insights
The myelin vacuolation (mv) rat shows impaired myelin production due to an attractin gene mutation. This study reveals defective myelinogenesis, not oligodendrocyte formation, in the central nervous system.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- The myelin vacuolation (mv) rat model displays hypomyelination and myelin vacuole formation in the central nervous system (CNS).
- These alterations are linked to a null mutation in the attractin gene and progress with postnatal development, primarily affecting white matter.
- Microglial activation is notably restricted to the gray matter in mv rats.
Purpose of the Study:
- To investigate the distribution and expression patterns of key CNS myelin proteins in the spinal cord of mv rats during myelin lesion development.
- To elucidate the cellular mechanisms underlying myelin defects in this model.
Main Methods:
- Immunohistochemistry and Western blot analysis to assess myelin protein expression.
- Real-time PCR to quantify proteolipid protein (PLP) mRNA levels.
- Oligodendrocyte cell counting to evaluate oligodendrocyte numbers.
Main Results:
- A significant reduction in major CNS myelin protein expression was observed in both white and gray matter of mv rats.
- Real-time PCR confirmed a substantial decrease in PLP mRNA expression in mv rat spinal cords.
- No significant difference in the number of PLP mRNA-positive oligodendrocytes was found between control and mv rats.
Conclusions:
- Myelin protein production by oligodendrocytes is impaired in mv rats, despite normal oligodendrocyte numbers.
- The study concludes that myelinogenesis, rather than oligodendrogenesis, is severely affected in both white and gray matter of the myelin vacuolation rat model.
- Attractin gene mutation impacts oligodendrocyte function, leading to hypomyelination.
