Improvement in dysmyelination by the inhibition of microglial activation in a mouse model of Sandhoff disease

Neuroreport
Yasuhiro OgawaKazuhiko Oishi

Abstract

Sandhoff disease (SD) is a genetic disorder caused by a mutation of the β-subunit gene β-hexosaminidase B (HexB) in humans, which results in the massive accumulation of the ganglioside GM2 and related glycosphingolipids in the nervous system. SD causes progressive neurodegeneration and changes in white matter in human infants. An animal model of SD has been established, Hexb-deficient (Hexb) mice, which shows abnormalities resembling the severe phenotype found in human infants. Previously, we reported that the activation state of microglia caused astrogliosis in the early stage of Hexb mouse development. To study how the symptoms of SD develop, we explored the difference in gene expression between 4-week-old Hexb and Hexb mouse cerebral cortices by microarray analysis. The data indicated not only the upregulation of immune system-related genes but also the downregulation of myelin-related genes in the 4-week-old Hexb mouse cerebral cortices. To test the correlation between inflammation and dysmyelination, we generated double-knockout mice of Hexb and the Fc receptor γ gene (Fcrγ), which is a regulator of autoimmune responses. Dysmyelination recovered in these double-knockout mice. The number of oligodendrocyte progenitors, whic...Continue Reading

References

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Jun 21, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Konrad Sandhoff, Klaus Harzer
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Feb 7, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yukari Shigemoto-MogamiKaoru Sato

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Citations

Jun 22, 2019·Annual Review of Biochemistry·Bernadette Breiden, Konrad Sandhoff

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Datasets Mentioned

BETA
GM2

Software Mentioned

Expression Console
AxioVision
GeneChip Operating Software
Photoshop
JMP pro
Proia
ImageJ
GeneSpring GX

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