AI Article Synopsis
- MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder linked to genetic duplications of the MECP2 gene and nearby genes like IRAK1.
- Existing mouse models for MDS often only express MECP2, limiting research potential.
- A new CRISPR/Cas9 tandem duplication mouse model called 'Mecp2 Dup' accurately mimics human MDS and shows significant neurobehavioral issues and immune response abnormalities, making it useful for studying the disorder and exploring therapies.
Article Abstract
MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1. Current MDS mouse models involve transgenic expression of MECP2 only, limiting their applicability to the study of the disease. Herein, we show that an efficient and precise CRISPR/Cas9 fusion proximity-based approach can be utilized to generate an Irak1-Mecp2 tandem duplication mouse model ('Mecp2 Dup'). The Mecp2 Dup mouse model recapitulates the genomic landscape of human MDS by harboring a 160 kb tandem duplication encompassing Mecp2 and Irak1, representing the minimal disease-causing duplication, and the neighboring genes Opn1mw and Tex28. The Mecp2 Dup model exhibits neuro-behavioral abnormalities, and an abnormal immune response to infection not previously observed in other mouse models, possibly owing to Irak1 overexpression. The Mecp2 Dup model thus provides a tool to investigate MDS disease mechanisms and develop potential therapies applicable to patients.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552499 | PMC |
| http://dx.doi.org/10.1242/dmm.050528 | DOI Listing |
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