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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 01, 2020 |
| Title |
Whole brain delivery of an instability-prone Mecp2 transgene improves behavioral and molecular pathological defects in mouse models of Rett syndrome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Rett syndrome is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy for this disease presents inherent hurdles since MECP2 is expressed throughout the brain and its duplication leads to severe neurological conditions as well. Herein, we use the AAV-PHP.eB to deliver an instability-prone Mecp2 (iMecp2) transgene cassette which, increasing RNA destabilization and inefficient protein translation of the viral Mecp2 transgene, limits supraphysiological Mecp2 protein levels. Intravenous injections of the PHP.eB-iMecp2 virus in symptomatic Mecp2 mutant mice significantly improved locomotor activity, lifespan and gene expression normalization. Remarkably, PHP.eB-iMecp2 administration was well tolerated in female Mecp2 mutant or in wild-type animals. In contrast, we observed a strong immune response to the transgene in treated male Mecp2 mutant mice that was overcome by immunosuppression. Overall, PHP.eB-mediated delivery of iMecp2 provided widespread and efficient gene transfer maintaining physiological Mecp2 protein levels in the brain.
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| Overall design |
3⨯ WT mice, 3⨯ MECP2 KO mice, 3⨯ gene therapy-treated WT mice, 3⨯ gene therapy-treated KO mice
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| Contributor(s) |
Broccoli V, Massimino L, Luoni M, Giannelli S |
| Citation(s) |
32207685 |
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| Submission date |
Jan 16, 2019 |
| Last update date |
Mar 30, 2020 |
| Contact name |
Luca Massimino |
| E-mail(s) |
admin@lucamassimino.com
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| Phone |
+393389039500
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| Organization name |
Ospedale San Raffaele
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| Department |
Gastroenterology
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| Street address |
Via Olgettina, 58
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| City |
Milano |
| State/province |
MI |
| ZIP/Postal code |
20100 |
| Country |
Italy |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA515413 |
| SRA |
SRP179721 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE125155_RAW.tar |
3.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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