Abstract
Niemann-Pick type C 1 (NPC1) disease is an autosomal recessive cholesterol transport defect resulting in a neurodegenerative process in patients mainly at an early age, although some patients may start with manifestation in adult. Since loss of myelin is considered as a main pathogenetic factor, the precise mechanism inducing dysmylination in NPC1 disease is still unclear. In the present study, a quantitative evaluation on the myelin protein and its regulatory factors of oligodendrocytes, such as SRY-related HMG-box 10 (Sox10), Yin Yang 1 factor (YY1) and myelin gene regulatory factor (MRF), in different parts of the brain and spinal cord was performed in NPC1-mutant mice. The results showed that NPC1 protein was expressed in oligodendrocytes and the amount of myelin protein was generally decreased in all parts of the brain and spinal cord in NPC1-mutant mice. Compared to wild type, the amount of Sox10 and YY1 was not different in NPC1-mutant mice, but MRF was significantly decreased, suggesting a possible mechanism perturbing differentiation of oligodendrocytes and the myelination process in the NPC1-mutant mouse.
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Abbreviations
- CB:
-
Cerebellum
- CNPase:
-
2′,3′-cyclic nucleotide-3′-phosphodiesterase
- CNS:
-
Central nervous system
- DH:
-
Dorsal horn
- E:
-
Embryonic day
- EC:
-
Olfactory ensheathing cells
- EPI:
-
External plexiform layer
- E/OV:
-
Extended amygdale and olfactory ventricle
- ER:
-
Endoplasmic reticulum
- FB:
-
Forebrain
- GAPDH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- Gl:
-
Glomerular layer
- GrO:
-
Granule cell layer
- HB:
-
Hindbrain
- IPI:
-
Internal plexiform layer
- MBP:
-
Myelin basic protein
- MI:
-
Mitral cell layer
- MRF:
-
Myelin gene regulatory factor
- NPC:
-
Niemann-Pick type C
- NPC1−/− :
-
NPC1-mutant
- OB:
-
Olfactory bulb
- OLs:
-
Myelinating oligdendrocytes
- OPCs:
-
Oligodendrocyte progenitor cells
- OPLs:
-
Postmitotic premyelinating oligodendrocytes
- P:
-
Postnatal day
- SOX10:
-
SRY-related HMG-box 10
- SP:
-
Spinal cord
- VH:
-
Ventral horn
- YY1:
-
Transcription factor Yin Yang 1
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Acknowledgements
This work is supported by an intramural FORUN program from School of Medicine University of Rostock.
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Yan, X., Lukas, J., Witt, M. et al. Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse. Metab Brain Dis 26, 299–306 (2011). https://doi.org/10.1007/s11011-011-9263-9
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DOI: https://doi.org/10.1007/s11011-011-9263-9