TBX1 Is Responsible for Cardiovascular Defects in velo-cardio-facial/DiGeorge Syndrome

Cell. 2001 Feb 23;104(4):619-29. doi: 10.1016/s0092-8674(01)00247-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cardiovascular Abnormalities / genetics
  • Chromosomes, Human, Pair 22
  • DiGeorge Syndrome / etiology*
  • DiGeorge Syndrome / genetics*
  • Flow Cytometry
  • Gene Library
  • Gene Targeting
  • Genotype
  • Humans
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Models, Genetic
  • Mutation
  • Parathyroid Glands / abnormalities
  • Phenotype
  • T-Box Domain Proteins / biosynthesis
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / physiology*
  • Thymus Gland / abnormalities
  • Time Factors

Substances

  • T-Box Domain Proteins
  • TBX1 protein, human
  • Tbx1 protein, mouse