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Targeting Sufu-mediated Gli transcription alleviates ciliopathic phenotypes [sufu_RNA-seq]

GSE301707 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2026/01/07 Platform GPL24247
Summary
Ciliopathies are incurable, pleiotropic diseases that result from defective cilia. Several ciliopathic phenotypes arise from improper processing and activity of Gli transcription factors yet attempts to rescue these phenotypes by overexpressing activator or repressor Gli isoforms have proven unsuccessful. Gli proteins are regulated by Sufu, and Sufu-Gli complexes accumulate in ciliopathies, fundamentally altering the normal Sufu-Gli interaction dynamics. Herein, we investigated whether targeting Sufu-Gli interactions would provide a therapeutic benefit for ciliopathies. We introduced a single copy of SufuD159R, a point mutation that disrupts Sufu-Gli binding, into a ciliopathic mouse model. This genetic modification restored Gli3 binding to DNA and the subsequent transcription of target genes, and led to a significant rescue of numerous ciliopathic phenotypes. These findings suggest that modulating Sufu-Gli interactions may serve as a promising therapeutic approach for ameliorating ciliopathic pathologies.
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Direct links to NCBI, no account and no request form: the whole study as GSE301707_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1283947 and SRA study SRP595895. Searching any of these in the dataset finder brings you back here.

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