DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1

@article{Jerome2001DiGeorgeSP,
  title={DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1},
  author={Loydie A. Jerome and Virginia E Papaioannou},
  journal={Nature Genetics},
  year={2001},
  volume={27},
  pages={286-291}
}
The DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a relatively common human disorder, usually associated with deletions of chromosome 22q11. The genetic basis for the wide range of developmental anomalies in the heart, glands and facial structures has been elusive. We have investigated the potential role of one candidate gene, Tbx1, which encodes a transcription factor of the T-box family, by producing a null mutation in mice. We found that mice heterozygous for the mutation had a high… Expand
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TLDR
Although deletion of the genes in the Lgdel region in mice may recapitulate some of the behavioral phenotypes seen in humans with VCFS/DGS, these phenotypes are not found in mice with complete loss of Gscl or in micewith heterozygous loss of Tbx1, suggesting that the neuropsychiatric and physical malformations of VCFS /DGS may act by different genetic mechanisms. Expand
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TLDR
A nonsynonymous mutation p.W118R is identified in T-box of TBX1, the DNA binding domain for transcription activity, which further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity ofTBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms. Expand
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Mutation analysis and creation of mouse models which mimic the human disorder have identified that the Tbx1 (T-box 1) transcription factor is the major dosage-sensitive gene in the deletion region and have allowed exploration of the underlying developmental pathways and signalling networks disrupted in these syndromes. Expand
Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects.
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It is proposed that overexpression of one or more of the transgenes is responsible for the etiology of the ear defects in the mice and TbX1 likely plays a central role. Expand
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A recurrent 370‐kb deletion at the 22q11.2 locus is identified as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Expand
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TLDR
Using mouse models of the congenital heart disease, it is found that reduced dosage of p53 suppresses the Tbx1 mutant phenotype and a strong genetic interaction between TbX1 and transformation related protein 53 (Trp53), which indicates a mechanism by which reduced p53, by genetic or pharmacological means, can counterbalance the consequences of reducing dosage of T bx1. Expand
DiGeorge syndrome, Tbx1, and retinoic acid signaling come full circle.
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  • Biology, Medicine
  • Circulation research
  • 2010
TLDR
A new functional link between Tbx1 and RA signaling in the regulation of aortic arch anomalies in a mouse model of DiGeorge syndrome is established in this issue of Circulation Research. Expand
The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans
TLDR
Using cell transplantation studies, it is demonstrated that vgo/tbx1 acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest-derived cartilages secondarily. Expand
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References

SHOWING 1-10 OF 29 REFERENCES
Congenital heart disease in mice deficient for the DiGeorge syndrome region
TLDR
The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. Expand
Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse.
TLDR
It is suggested that heterozygous deletion of this portion of the DGCR is sufficient for sensorimotor gating abnormalities, but not sufficient to produce the common features of DGS/VCFS in the mouse. Expand
Normal cardiovascular development in mice deficient for 16 genes in 550 kb of the velocardiofacial/DiGeorge syndrome region.
TLDR
A strategy for selecting cell lines with defined chromosomal rearrangements based on reconstitution of a dominant selection marker after Cre-mediated recombination of LoxP sites is described, which should be widely applicable to many cell lines. Expand
Goosecoid-like (Gscl), a candidate gene for velocardiofacial syndrome, is not essential for normal mouse development.
TLDR
Although the gene inactivation experiments indicate that haploinsufficiency for GSCL is unlikely to be the sole cause of the developmental field defect thought to be responsible for many of the abnormalities in VCFS/DGS patients, its localized expression during development could suggest that hemizygosity forGSCL, in combination with hemizykosity for other genes in 22q11, contributes to some of thedevelopmental defects as well as the behavioral anomalies seen in these patients. Expand
Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene.
TLDR
The identification, cloning, and characterization of the human TBX1 gene is described, which maps to the center of the DiGeorge chromosomal region, and the mouse cDNA sequence is extended to permit comparisons between human and mouse Tbx1. Expand
Functional analysis of Gscl in the pathogenesis of the DiGeorge and velocardiofacial syndromes.
TLDR
The genomic location of Gscl and its expression in a subset of the tissues affected in DGS/VCFS patients suggest that Gscl may contribute to the pathogenesis of DGS /VCFS. Expand
The murine homologue of HIRA, a DiGeorge syndrome candidate gene, is expressed in embryonic structures affected in human CATCH22 patients.
TLDR
The isolation of several murine embryonic cDNAs of the DiGeorge syndrome candidate gene HIRA are reported and sequence analysis reveals that Hira bears homology to the p60 subunit of the human Chromatin Assembly Factor I and yeast hir1p and Hir2p, suggesting that H Kira might have some role in chromatin assembly and/or histone regulation. Expand
Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification
TLDR
It is suggested that PFM and craniosynostosis result, respectively, from loss and gain of activity in an MSX2-mediated pathway of calvarial osteogenic differentiation. Expand
The 22q11 deletion syndromes.
  • P. Scambler
  • Biology, Medicine
  • Human molecular genetics
  • 2000
TLDR
Current efforts are directed at the study of engineered chromosome mouse models which offer the potential to dissect at least some of the developmental pathways disrupted in this intriguing group of malformation syndromes. Expand
Cloning and developmental expression analysis of chick Hira (Chira), a candidate gene for DiGeorge syndrome.
TLDR
HIRA is expressed in the developing neural plate, the neural tube, neural crest and the mesenchyme of the head and branchial arch structures and may have a role in the haploinsufficiency syndromes caused by deletion of 22q11. Expand
...
1
2
3
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