TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome

Sandra Merscher; Birgit Funke; Jonathan A. Epstein; Joerg Heyer; Anne Puech; Min Min Lu; Ramnik J. Xavier; Marie B. Demay; Robert G. Russell; Stephen Factor; Kazuhito Tokooya; Bruno St Jore; Melissa Lopez; Raj K. Pandita; Marie Lia; Danaise Carrion; Hui Xu; Hubert Schorle; James B. Kobler; Peter Scambler; Anthony Wynshaw-Boris; Arthur I. Skoultchi; Bernice E. Morrow; Raju Kucherlapati

doi:10.1016/S0092-8674(01)00247-1

TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome

Sandra Merscher, Birgit Funke, Jonathan A. Epstein, Joerg Heyer, Anne Puech, Min Min Lu, Ramnik J. Xavier, Marie B. Demay, Robert G. Russell, Stephen Factor, Kazuhito Tokooya, Bruno St Jore, Melissa Lopez, Raj K. Pandita, Marie Lia, Danaise Carrion, Hui Xu, Hubert Schorle, James B. Kobler, Peter ScamblerAnthony Wynshaw-Boris, Arthur I. Skoultchi, Bernice E. Morrow, Raju Kucherlapati

Research output: Contribution to journal › Article › peer-review

780 Scopus citations

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.

Original language	English (US)
Pages (from-to)	619-629
Number of pages	11
Journal	Cell
Volume	104
Issue number	4
DOIs	https://doi.org/10.1016/S0092-8674(01)00247-1
State	Published - Feb 23 2001

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/S0092-8674(01)00247-1

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Merscher, S., Funke, B., Epstein, J. A., Heyer, J., Puech, A., Lu, M. M., Xavier, R. J., Demay, M. B., Russell, R. G., Factor, S., Tokooya, K., Jore, B. S., Lopez, M., Pandita, R. K., Lia, M., Carrion, D., Xu, H., Schorle, H., Kobler, J. B., ... Kucherlapati, R. (2001). TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell, 104(4), 619-629. https://doi.org/10.1016/S0092-8674(01)00247-1

Merscher, S, Funke, B, Epstein, JA, Heyer, J, Puech, A, Lu, MM, Xavier, RJ, Demay, MB, Russell, RG, Factor, S, Tokooya, K, Jore, BS, Lopez, M, Pandita, RK, Lia, M, Carrion, D, Xu, H, Schorle, H, Kobler, JB, Scambler, P, Wynshaw-Boris, A, Skoultchi, AI , Morrow, BE & Kucherlapati, R 2001, 'TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome', Cell, vol. 104, no. 4, pp. 619-629. https://doi.org/10.1016/S0092-8674(01)00247-1

@article{af5cd53d250741e98f55ddc2bc2dbed3,

title = "TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome",

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.",

author = "Sandra Merscher and Birgit Funke and Epstein, {Jonathan A.} and Joerg Heyer and Anne Puech and Lu, {Min Min} and Xavier, {Ramnik J.} and Demay, {Marie B.} and Russell, {Robert G.} and Stephen Factor and Kazuhito Tokooya and Jore, {Bruno St} and Melissa Lopez and Pandita, {Raj K.} and Marie Lia and Danaise Carrion and Hui Xu and Hubert Schorle and Kobler, {James B.} and Peter Scambler and Anthony Wynshaw-Boris and Skoultchi, {Arthur I.} and Morrow, {Bernice E.} and Raju Kucherlapati",

note = "Funding Information: The work described here was inspired by Robert Shprintzen and Rosalie Goldberg. We thank J. Horner and K. Chen for microinjections, L. Edelmann and T. Van De Water for scientific discussions, and J. Sterio for technical assistance. This work is supported by grants from the NIH (HD34980 to R. K., B. E. M., and A. I. S.; HL 61475, HL 62974 to J. A. E.; AI01472 to R. J. X.), the WW Smith Chartitable Trust (J. A. E.), the American Heart Association (B. M.), the British Heart Foundation (P. J. S.), and the Deutsche Forschungsgemeinschaft (H. S.).",

year = "2001",

month = feb,

day = "23",

doi = "10.1016/S0092-8674(01)00247-1",

language = "English (US)",

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pages = "619--629",

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T1 - TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome

AU - Merscher, Sandra

AU - Funke, Birgit

AU - Epstein, Jonathan A.

AU - Heyer, Joerg

AU - Puech, Anne

AU - Lu, Min Min

AU - Xavier, Ramnik J.

AU - Demay, Marie B.

AU - Russell, Robert G.

AU - Factor, Stephen

AU - Tokooya, Kazuhito

AU - Jore, Bruno St

AU - Lopez, Melissa

AU - Pandita, Raj K.

AU - Lia, Marie

AU - Carrion, Danaise

AU - Xu, Hui

AU - Schorle, Hubert

AU - Kobler, James B.

AU - Scambler, Peter

AU - Wynshaw-Boris, Anthony

AU - Skoultchi, Arthur I.

AU - Morrow, Bernice E.

AU - Kucherlapati, Raju

N1 - Funding Information: The work described here was inspired by Robert Shprintzen and Rosalie Goldberg. We thank J. Horner and K. Chen for microinjections, L. Edelmann and T. Van De Water for scientific discussions, and J. Sterio for technical assistance. This work is supported by grants from the NIH (HD34980 to R. K., B. E. M., and A. I. S.; HL 61475, HL 62974 to J. A. E.; AI01472 to R. J. X.), the WW Smith Chartitable Trust (J. A. E.), the American Heart Association (B. M.), the British Heart Foundation (P. J. S.), and the Deutsche Forschungsgemeinschaft (H. S.).

PY - 2001/2/23

Y1 - 2001/2/23

N2 - 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.

AB - 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.

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AN - SCOPUS:17744395906

SN - 0092-8674

VL - 104

SP - 619

EP - 629

JO - Cell

JF - Cell

IS - 4

ER -

TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome

Abstract

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