Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice.
<h4>Background</h4>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.<h4>Methods</h4>Differential gene expression in vehicle-exposed mouse brain was determine...
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doaj-846361f0c7914ccdb0167d0d732e4d682021-03-04T11:11:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011510e023953710.1371/journal.pone.0239537Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice.Joelle MakoukjiSally El-SittNadine J MakhoulJihane SoueidHumam KadaraRose-Mary Boustany<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Analysis identified 66 genes in male and 30 in female brains differentially expressed in GalCer-treated versus vehicle-exposed Cln3Δex7/8 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.<h4>Conclusions</h4>This study sheds light on global expression patterns following GalCer treatment of Cln3Δex7/8 mice. Understanding molecular effects of GalCer on mouse brain gene expression, paves the way for personalized strategies for treating this debilitating disease in humans.https://doi.org/10.1371/journal.pone.0239537 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joelle Makoukji Sally El-Sitt Nadine J Makhoul Jihane Soueid Humam Kadara Rose-Mary Boustany |
spellingShingle |
Joelle Makoukji Sally El-Sitt Nadine J Makhoul Jihane Soueid Humam Kadara Rose-Mary Boustany Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice. PLoS ONE |
author_facet |
Joelle Makoukji Sally El-Sitt Nadine J Makhoul Jihane Soueid Humam Kadara Rose-Mary Boustany |
author_sort |
Joelle Makoukji |
title |
Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice. |
title_short |
Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice. |
title_full |
Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice. |
title_fullStr |
Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice. |
title_full_unstemmed |
Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice. |
title_sort |
sex differences in gene expression with galactosylceramide treatment in cln3δex7/8 mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Analysis identified 66 genes in male and 30 in female brains differentially expressed in GalCer-treated versus vehicle-exposed Cln3Δex7/8 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.<h4>Conclusions</h4>This study sheds light on global expression patterns following GalCer treatment of Cln3Δex7/8 mice. Understanding molecular effects of GalCer on mouse brain gene expression, paves the way for personalized strategies for treating this debilitating disease in humans. |
url |
https://doi.org/10.1371/journal.pone.0239537 |
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