Abstract
Williams-Beuren syndrome (WBS) is a relatively rare disease caused by the deletion of 1.5 to 1.8 Mb on chromosome 7 which contains approximately 28 genes. This multisystem disorder is mainly characterized by supravalvular aortic stenosis, mental retardation, and distinctive facial features. We generated mouse embryonic stem (ES) cells clones expressing each of the 4 human WBS genes (WBSCR1, GTF2I, GTF2IRD1 and GTF2IRD2) found in the specific delated region 7q11.23 causative of the WBS. We generated at least three stable clones for each gene with stable integration in the ROSA26 locus of a tetracycline-inducible upstream of the coding sequence of the genet tagged with a 3xFLAG epitope. Three clones for each gene were transcriptionally profiled in inducing versus non-inducing conditions for a total of 24 profiles. This small collection of human WBS-ES cell clones represents a resource to facilitate the study of the function of these genes during differentiation.
Highlights
Background & SummaryWilliams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by a hemizygous deletion of 1.5 Mb segment occurring in approximately 95% of cases and a larger 1.84 Mb deletion observed in about 1 of 20 cases[1,2]
The first genome-wide transcription study performed in primary fibroblasts from eight individuals with Williams-Beuren syndrome (WBS) resulted in set of candidate pathways mis-regulated in WBS possibly involved in associated phenotypes[2]
To facilitate the study of genes involved in WBS, we generated and transcriptionally profiled of mouse embryonic stem (ES) cells[11,12] with inducible expression of the three GTF-transcription factors (GTF2IRD1, GTF2IRD2 and GTF2I) together with the translation initiation factor Eif4h
Summary
Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by a hemizygous deletion of 1.5 Mb segment occurring in approximately 95% of cases and a larger 1.84 Mb deletion observed in about 1 of 20 cases[1,2]. To facilitate the study of genes involved in WBS, we generated and transcriptionally profiled of mouse embryonic stem (ES) cells[11,12] with inducible expression of the three GTF-transcription factors (GTF2IRD1, GTF2IRD2 and GTF2I) together with the translation initiation factor Eif4h Targeted Gtf2IRD1 knockout mouse is known to cause the up-regulation of growth factors and other genes involved in brain development and cellular proliferation which may be linked with the extreme thickening of the epidermis observed in the mouse model[20]. Total RNA was profiled by Affimetrix microarrays (the whole set of results is available in the GEO database [GSE9670124])[25,26] This analysis was performed to detect differentially expressed genes (that is, in induced versus non-induced cells, Supplementary Fig. 4) in ES cells modeling the WBS
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