Reduced Granule Cell Proliferation and Molecular Dysregulation in the Cerebellum of Lysosomal Acid Phosphatase 2 (ACP2) Mutant Mice
Lysosomal acid phosphatase 2 (<i>Acp2</i>) mutant mice (naked-ataxia, <i>nax</i>) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays,...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/6/2994 |
| Summary: | Lysosomal acid phosphatase 2 (<i>Acp2</i>) mutant mice (naked-ataxia, <i>nax</i>) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays, and RT-qPCR, we show downregulation of MYCN and dysregulation of the SHH signaling pathway in the <i>nax</i> cerebellum. MYCN protein expression is significantly reduced at P10, but not at the peak of proliferation at around P6 when the number of granule cells is strikingly reduced in the <i>nax</i> cerebellum. Despite the significant role of the SHH–MycN pathway in granule cell proliferation, our study suggests that a broader molecular pathway and additional mechanisms regulating granule cell development during the clonal expansion period are impaired in the <i>nax</i> cerebellum. In particular, our results indicate that downregulation of the protein synthesis machinery may contribute to the reduced number of granule cells in the <i>nax</i> cerebellum. |
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| ISSN: | 1661-6596 1422-0067 |