GTF2IRD1 in Craniofacial Development of Humans and Mice

@article{Tassabehji2005GTF2IRD1IC,
  title={GTF2IRD1 in Craniofacial Development of Humans and Mice},
  author={May Tassabehji and Peter Hammond and Annette Karmiloff-Smith and Pamela Thompson and Snorri Thorgeirsson and Marian E Durkin and Nicholas C. Popescu and Timothy J. Hutton and Kay A. Metcalfe and Agnes K Rucka and Helen Stewart and Andrew P. Read and Mark Maconochie and Dian Donnai},
  journal={Science},
  year={2005},
  volume={310},
  pages={1184 - 1187}
}
Craniofacial abnormalities account for about one-third of all human congenital defects, but our understanding of the genetic mechanisms governing craniofacial development is incomplete. We show that GTF2IRD1 is a genetic determinant of mammalian craniofacial and cognitive development, and we implicate another member of the TFII-I transcription factor family, GTF2I, in both aspects. Gtf2ird1-null mice exhibit phenotypic abnormalities reminiscent of the human microdeletion disorder Williams… 

Gtf2i and Gtf2ird1 mutation do not account for the full phenotypic effect of the Williams syndrome critical region in mouse models.

It is shown that the complete deletion model has deficits across several behavioral domains including social communication, motor functioning, and conditioned fear that are not explained by loss of function mutations in Gtf2i and GTF2ird1.

Gtf2i and Gtf2ird1 mutation are not sufficient to reproduce mouse phenotypes caused by the Williams Syndrome critical region

It is shown that the complete deletion model has deficits across several behavioral domains including social communication, motor functioning, and conditioned fear that are not explained by loss of function mutations in Gtf2i and GTF2ird1.

Global Analysis of Gene Expression in the Developing Brain of Gtf2ird1 Knockout Mice

It is shown that differences in expression of genes on chromosome 5 were the result of retention of that chromosome region from the targeted embryonic stem cell line, and so were dependent upon strain rather than Gtf2ird1 genotype.

RNA-Seq analysis of Gtf2ird1 knockout epidermal tissue provides potential insights into molecular mechanisms underpinning Williams-Beuren syndrome

Gtf2ird1 inactivation results in widespread gene dysregulation, some of which may be due to the secondary consequences of gene regulatory network disruptions involving several transcription factors and signalling molecules.

Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike.

The complicated control of the penetrance for one phenotype in SMS mouse models provides tools to elucidate molecular mechanisms for penetrance and clearly shows that a null allele caused by chromosomal deletion can have different phenotypic consequences than one caused by gene inactivation.

Heterozygous deletion of the Williams-Beuren syndrome critical interval in mice recapitulates most features of the human disorder.

These mice recapitulate most crucial phenotypes of the human disorder, provide novel insights into the pathophysiological mechanisms of the disease such as the neural substrates of the behavioral manifestations, and will be valuable to evaluate novel therapeutic approaches.

Cdh1 regulates craniofacial development via APC-dependent ubiquitination and activation of Goosecoid

This study reveals a novel role for Cdh1 in craniofacial development through promoting APC-dependent non-proteolytic ubiquitination and activation of Gsc and reports that Gsc is also ubiquitinated and activated by the APCCdh1 E3 ubiquitin ligase, leading to transcriptional activation of various Gsc target genes crucial for cranioFacial development.

Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions

It is found that homozygous deletion of Gtf2i causes lethality during embryonic development with neural tube closure defects and exencephaly, consistent with other reports, and that GTF2I haploinsufficiency could be a contributor to the hypersociability in WBS patients.
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