Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder
Summary: Autism spectrum disorders (ASDs) involve social, communication, and behavioral challenges. ASDs display a remarkable sex difference with a 4:1 male to female prevalence ratio; however, the underlying mechanism remains largely unknown. Using the UBE3A-overexpressing mouse model for ASD, we s...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001282 |
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| author | Yuan Tian Hui Qiao KathrynAnn Odamah Ling-Qiang Zhu Heng-Ye Man |
| author_facet | Yuan Tian Hui Qiao KathrynAnn Odamah Ling-Qiang Zhu Heng-Ye Man |
| author_sort | Yuan Tian |
| collection | DOAJ |
| description | Summary: Autism spectrum disorders (ASDs) involve social, communication, and behavioral challenges. ASDs display a remarkable sex difference with a 4:1 male to female prevalence ratio; however, the underlying mechanism remains largely unknown. Using the UBE3A-overexpressing mouse model for ASD, we studied sexually dimorphic changes at behavioral, genetic, and molecular levels. We found that male mice with extra copies of Ube3A exhibited greater impairments in social communication, long-term memory, and pain sensitivity compared to females. UBE3A-mediated degradation reduced androgen receptor (AR) levels in both sexes but only male mice showed significant dysregulation in the expression of AR target genes. Importantly, restoring AR levels in the brain normalized levels of AR target genes, and rescued the deficits in social preference, grooming, and memory in male UBE3A-overexpressing mice, without affecting females. These findings reveal the critical role of AR signaling in sex-specific changes linked to UBE3A-dependent ASD. |
| format | Article |
| id | doaj-art-4e953e0fb55d45d2908d7ca839135db1 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-4e953e0fb55d45d2908d7ca839135db12025-02-05T04:32:33ZengElsevieriScience2589-00422025-02-01282111868Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorderYuan Tian0Hui Qiao1KathrynAnn Odamah2Ling-Qiang Zhu3Heng-Ye Man4Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USADepartment of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, ChinaDepartment of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA; Department of Pharmacology, Physiology & Biophysics, Boston University School of Medicine, 72 East Concord St., Boston, MA 02118, USA; Center for Systems Neuroscience, Boston University, 610 Commonwealth Avenue, Boston, MA 02215, USA; Corresponding authorSummary: Autism spectrum disorders (ASDs) involve social, communication, and behavioral challenges. ASDs display a remarkable sex difference with a 4:1 male to female prevalence ratio; however, the underlying mechanism remains largely unknown. Using the UBE3A-overexpressing mouse model for ASD, we studied sexually dimorphic changes at behavioral, genetic, and molecular levels. We found that male mice with extra copies of Ube3A exhibited greater impairments in social communication, long-term memory, and pain sensitivity compared to females. UBE3A-mediated degradation reduced androgen receptor (AR) levels in both sexes but only male mice showed significant dysregulation in the expression of AR target genes. Importantly, restoring AR levels in the brain normalized levels of AR target genes, and rescued the deficits in social preference, grooming, and memory in male UBE3A-overexpressing mice, without affecting females. These findings reveal the critical role of AR signaling in sex-specific changes linked to UBE3A-dependent ASD.http://www.sciencedirect.com/science/article/pii/S2589004225001282Human geneticsMolecular neuroscience |
| spellingShingle | Yuan Tian Hui Qiao KathrynAnn Odamah Ling-Qiang Zhu Heng-Ye Man Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder iScience Human genetics Molecular neuroscience |
| title | Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder |
| title_full | Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder |
| title_fullStr | Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder |
| title_full_unstemmed | Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder |
| title_short | Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder |
| title_sort | role of androgen receptors in sexually dimorphic phenotypes in ube3a dependent autism spectrum disorder |
| topic | Human genetics Molecular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001282 |
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