Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice

@article{Lindsay2001Tbx1HI,
  title={Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice},
  author={Elizabeth A. Lindsay and Francesca Vitelli and Hong Su and Masae Morishima and Tuong Huynh and Tiziano Pramparo and Vesna Jurecic and George Ogunrinu and Helen F. Sutherland and Peter J. Scambler and Allan Bradley and Antonio Baldini},
  journal={Nature},
  year={2001},
  volume={410},
  pages={97-101}
}
DiGeorge syndrome is characterized by cardiovascular, thymus and parathyroid defects and craniofacial anomalies, and is usually caused by a heterozygous deletion of chromosomal region 22q11.2 (del22q11) (ref. 1). A targeted, heterozygous deletion, named Df(16)1, encompassing around 1 megabase of the homologous region in mouse causes cardiovascular abnormalities characteristic of the human disease. Here we have used a combination of chromosome engineering and P1 artificial chromosome… Expand
22q11 Deletion Syndrome: A Role for Tbx1 in Pharynx and Cardiovascular Development
TLDR
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
Dissecting contiguous gene defects: TBX1.
  • A. Baldini
  • Biology, Medicine
  • Current opinion in genetics & development
  • 2005
TLDR
Tbx1 is an excellent tool to probe the genetic network governing embryonic pharyngeal development and is the only gene that, after an extensive functional analysis in the mouse, has been found to be haploinsufficient. Expand
The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of TBX1
TLDR
Patients reaching adolescence and adulthood have a predisposition to psychiatric illness, and knowledge of the genetic and developmental mechanisms underlying 22q11DS has the potential to inform about common disease as well as developmental defect. Expand
Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice.
TLDR
Screening for chromosome rearrangements in patients suspected of VCFS, but who lacked a 22q11 deletion or TBX1 mutation found that biallelic expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal PAA development. Expand
VEGF: A modifier of the del22q11 (DiGeorge) syndrome?
TLDR
It is reported that absence of the Vegf164 isoform caused birth defects in mice, reminiscent of those found in del22q11 patients, and genetic data in mouse, fish and human indicate that VEGF is a modifier of cardiovascular birth defect in the del 22q11 syndrome. Expand
DiGeorge syndrome, Tbx1, and retinoic acid signaling come full circle.
  • K. Yutzey
  • 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
Wrapping Up DiGeorge Syndrome in a T-box?
TLDR
Investigators used “knockout” mice to study genes deleted in DGS/VCFS and suggest that human TBX1 haploin-sufficiency via chromosome 22q11 dele-tion plays a major role in human DGS-VCFS conotruncal defects. Expand
22q11 Deletion Syndrome: A Role for TBX1 in Pharyngeal and Cardiovascular Development
TLDR
The tissue specific and temporal requirements for Tbx1 are summarised, and what is know about the developmental pathways under its control is synthesised. Expand
p53 suppression partially rescues the mutant phenotype in mouse models of DiGeorge syndrome
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
Genetic Drivers of Kidney Defects in the DiGeorge Syndrome
TLDR
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
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 56 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
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
A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region.
TLDR
Synteny is document between a 150-kb region on mouse chromosome 16 and the most commonly deleted portion of chromosome 22q11.2.2 to recapitulate the developmental field defects characteristic of this syndrome. Expand
Cloning and comparative mapping of the DiGeorge syndrome critical region in the mouse.
TLDR
This work has mapped 19 murine homologues of genes and nine EST groups from the region deleted in DiGeorge syndrome and found them to be linked on mouse chromosome 16, confirming and extending previous analyses and the contig resources toward the generation of targeted deletions in the mouse. 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
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
Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome
TLDR
It is argued that DGS/VCFS results from haploinsufficiency secondary to a complex and as yet unexplained molecular mechanism, probably involving chromatin effects in mediating gene expression throughout the entire region. Expand
Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family
TLDR
Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBXS in heart and limb, consistent with a role in human embryonic development. Expand
Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR).
TLDR
This work reports on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. Expand
Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization.
TLDR
The results show that the instability of the 22q11 region is not restricted to humans but may have been present throughout evolution and underscore the importance of detailed comparative mapping of genes in mice and humans as a prerequisite for the development of mouse models of human diseases involving chromosomal rearrangements. Expand
...
1
2
3
4
5
...