TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.
Velo-cardio-facial syndrome (VCFS)/DiGeorge syndrome (DGS) is a human disorder characterized by a number of phenotypic features including cardiovascular defects. Most VCFS/DGS patients are hemizygous for a 1.5-3.0 Mb region of 22q11. To investigate the etiology of this disorder, we used a cre-loxP strategy to generate mice that are hemizygous for a 1.5 Mb deletion corresponding to that on 22q11. These mice exhibit significant perinatal lethality and have conotruncal and parathyroid defects. The conotruncal defects can be partially rescued by a human BAC containing the TBX1 gene. Mice heterozygous for a null mutation in Tbx1 develop conotruncal defects. These results together with the expression patterns of Tbx1 suggest a major role for this gene in the molecular etiology of VCFS/DGS.
Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461, Bronx, NY, USA
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Merscher
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Funke
J A
JA
Epstein
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Heyer
A
A
Puech
M M
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Lu
R J
RJ
Xavier
M B
MB
Demay
R G
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Russell
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Factor
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Tokooya
B S
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Jore
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Lopez
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Pandita
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Lia
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Carrion
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Xu
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Schorle
J B
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Kobler
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Scambler
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Wynshaw-Boris
A I
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Skoultchi
B E
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Morrow
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Kucherlapati
D000818:Animals; D018376:Cardiovascular Abnormalities / Q000235:genetics; D002892:Chromosomes, Human, Pair 22; D004062:DiGeorge Syndrome / Q000209:etiology* / Q000235:genetics*; D005434:Flow Cytometry; D015723:Gene Library; D018390:Gene Targeting; D005838:Genotype; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009154:Mutation; D010280:Parathyroid Glands / Q000002:abnormalities; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D013950:Thymus Gland / Q000002:abnormalities; D013997:Time Factors
D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; C491573:Tbx1 protein, mouse