| First Author | Makoukji J | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 10 | Pages | e0239537 |
| PubMed ID | 33006978 | Mgi Jnum | J:296280 |
| Mgi Id | MGI:6466599 | Doi | 10.1371/journal.pone.0239537 |
| Citation | Makoukji J, et al. (2020) Sex differences in gene expression with galactosylceramide treatment in Cln3Deltaex7/8 mice. PLoS One 15(10):e0239537 |
| abstractText | BACKGROUND: CLN3 disease is caused by mutations in the CLN3 gene. The purpose of this study is to discern global expression patterns reflecting therapeutic targets in CLN3 disease. METHODS: Differential gene expression in vehicle-exposed mouse brain was determined after intraperitoneal vehicle/Galactosylceramide (GalCer) injections for 40 weeks with GeneChip Mouse Genome 430 2.0 arrays. RESULTS: Analysis identified 66 genes in male and 30 in female brains differentially expressed in GalCer-treated versus vehicle-exposed Cln3Deltaex7/8 mice. Gene ontology revealed aberrations of biological function including developmental, cellular, and behavioral processes. GalCer treatment altered pathways of long-term potentiation/depression, estrogen signaling, synaptic vesicle cycle, ErbB signaling, and prion diseases in males, but prolactin signaling, selenium compound metabolism and steroid biosynthesis in females. Gene-gene network analysis highlighted networks functionally pertinent to GalCer treatment encompassing motor dysfunction, neurodegeneration, memory disorder, inflammation and astrogliosis in males, and, cataracts, inflammation, astrogliosis, and anxiety in females. CONCLUSIONS: This study sheds light on global expression patterns following GalCer treatment of Cln3Deltaex7/8 mice. Understanding molecular effects of GalCer on mouse brain gene expression, paves the way for personalized strategies for treating this debilitating disease in humans. |
