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

Author

Listed:
  • Elizabeth A. Lindsay

    (Departments of Pediatrics (Cardiology))

  • Francesca Vitelli

    (Departments of Pediatrics (Cardiology))

  • Hong Su

    (Baylor College of Medicine
    Human Genetics, Baylor College of Medicine)

  • Masae Morishima

    (Departments of Pediatrics (Cardiology))

  • Tuong Huynh

    (Departments of Pediatrics (Cardiology))

  • Tiziano Pramparo

    (Departments of Pediatrics (Cardiology))

  • Vesna Jurecic

    (University of Miami School of Medicine)

  • George Ogunrinu

    (University of Texas M. D. Anderson Cancer Center)

  • Helen F. Sutherland

    (Institute of Child Health)

  • Peter J. Scambler

    (Institute of Child Health)

  • Allan Bradley

    (Baylor College of Medicine
    Human Genetics, Baylor College of Medicine
    Sanger Centre
    Howard Hughest Medical Institute)

  • Antonio Baldini

    (Departments of Pediatrics (Cardiology)
    Baylor College of Medicine
    Human Genetics, Baylor College of Medicine)

Abstract

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 disease2. Here we have used a combination of chromosome engineering and P1 artificial chromosome transgenesis to localize the haploinsufficient gene in the region, Tbx1. We show that Tbx1, a member of the T-box transcription factor family, is required for normal development of the pharyngeal arch arteries in a gene dosage-dependent manner. Deletion of one copy of Tbx1 affects the development of the fourth pharyngeal arch arteries, whereas homozygous mutation severely disrupts the pharyngeal arch artery system. Our data show that haploinsufficiency of Tbx1 is sufficient to generate at least one important component of the DiGeorge syndrome phenotype in mice, and demonstrate the suitability of the mouse for the genetic dissection of microdeletion syndromes.

Suggested Citation

  • Elizabeth A. Lindsay & Francesca Vitelli & Hong Su & Masae Morishima & Tuong Huynh & Tiziano Pramparo & Vesna Jurecic & George Ogunrinu & Helen F. Sutherland & Peter J. Scambler & Allan Bradley & Anto, 2001. "Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice," Nature, Nature, vol. 410(6824), pages 97-101, March.
    • Handle: RePEc:nat:nature:v:410:y:2001:i:6824:d:10.1038_35065105
    DOI: 10.1038/35065105
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    Cited by:

    1. Christopher Bono & Yang Liu & Alexander Ferrena & Aneesa Valentine & Deyou Zheng & Bernice E. Morrow, 2023. "Single-cell transcriptomics uncovers a non-autonomous Tbx1-dependent genetic program controlling cardiac neural crest cell development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Hiroko Nomaru & Yang Liu & Christopher De Bono & Dario Righelli & Andrea Cirino & Wei Wang & Hansoo Song & Silvia E. Racedo & Anelisa G. Dantas & Lu Zhang & Chen-Leng Cai & Claudia Angelini & Lionel C, 2021. "Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm," Nature Communications, Nature, vol. 12(1), pages 1-19, December.

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