A murine model of Holt-Oram syndrome defines roles of the T-box transcription
factor Tbx5 in cardiogenesis and disease
B. Bruneau, G. Nemer, J. Schmitt, F. Charron, L. Robitaille, S. Caron, D. Conner, M. Gessler, M. Nemer, C. Seidman, и J. Seidman. Cell, 106 (6):
709-21(сентября 2001)Bruneau, B G Nemer, G Schmitt, J P Charron, F Robitaille, L Caron,
S Conner, D A Gessler, M Nemer, M Seidman, C E Seidman, J G S10 RR14792/RR/NCRR
NIH HHS/United States Research Support, Non-U.S. Gov't Research Support,
U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United
States Cell Cell. 2001 Sep 21;106(6):709-21..
Аннотация
Heterozygous Tbx5(del/+) mice were generated to study the mechanisms
by which TBX5 haploinsufficiency causes cardiac and forelimb abnormalities
seen in Holt-Oram syndrome. Tbx5 deficiency in homozygous mice (Tbx5(del/del))
decreased expression of multiple genes and caused severe hypoplasia
of posterior domains in the developing heart. Surprisingly, Tbx5
haploinsufficiency also markedly decreased atrial natriuretic factor
(ANF) and connexin 40 (cx40) transcription, implicating these as
Tbx5 target genes and providing a mechanism by which 50% reduction
of T-box transcription factors cause disease. Direct and cooperative
transactivation of the ANF and cx40 promoters by Tbx5 and the homeodomain
transcription factor Nkx2-5 was also demonstrated. These studies
provide one potential explanation for Holt-Oram syndrome conduction
system defects, suggest mechanisms for intrafamilial phenotypic variability,
and account for related cardiac malformations caused by other transcription
factor mutations.
Bruneau, B G Nemer, G Schmitt, J P Charron, F Robitaille, L Caron,
S Conner, D A Gessler, M Nemer, M Seidman, C E Seidman, J G S10 RR14792/RR/NCRR
NIH HHS/United States Research Support, Non-U.S. Gov't Research Support,
U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United
States Cell Cell. 2001 Sep 21;106(6):709-21.
%0 Journal Article
%1 Bruneau2001
%A Bruneau, B. G.
%A Nemer, G.
%A Schmitt, J. P.
%A Charron, F.
%A Robitaille, L.
%A Caron, S.
%A Conner, D. A.
%A Gessler, M.
%A Nemer, M.
%A Seidman, C. E.
%A Seidman, J. G.
%D 2001
%J Cell
%K Abnormalities, Acid Aging Alignment Animal Animals Atrial Base Binding Bone Cell Congenital/*genetics/physiopathology Connexins/genetics Data Defects, Development Development/genetics/*physiology Differentiation Disease Domain Electrocardiography Embryonic Factor/*genetics Fetal Forelimb/abnormalities Genetic Heart Heart/embryology Heterozygote Homology, Homozygote Humans Knockout Mice Models, Molecular Multiple/*genetics Myocardium/cytology Natriuretic Nucleic Promoter Proteins/deficiency/*genetics Rats Regions, Sequence Sheep Sites Syndrome T-Box and
%N 6
%P 709-21
%T A murine model of Holt-Oram syndrome defines roles of the T-box transcription
factor Tbx5 in cardiogenesis and disease
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11572777
%V 106
%X Heterozygous Tbx5(del/+) mice were generated to study the mechanisms
by which TBX5 haploinsufficiency causes cardiac and forelimb abnormalities
seen in Holt-Oram syndrome. Tbx5 deficiency in homozygous mice (Tbx5(del/del))
decreased expression of multiple genes and caused severe hypoplasia
of posterior domains in the developing heart. Surprisingly, Tbx5
haploinsufficiency also markedly decreased atrial natriuretic factor
(ANF) and connexin 40 (cx40) transcription, implicating these as
Tbx5 target genes and providing a mechanism by which 50% reduction
of T-box transcription factors cause disease. Direct and cooperative
transactivation of the ANF and cx40 promoters by Tbx5 and the homeodomain
transcription factor Nkx2-5 was also demonstrated. These studies
provide one potential explanation for Holt-Oram syndrome conduction
system defects, suggest mechanisms for intrafamilial phenotypic variability,
and account for related cardiac malformations caused by other transcription
factor mutations.
@article{Bruneau2001,
abstract = {Heterozygous Tbx5(del/+) mice were generated to study the mechanisms
by which TBX5 haploinsufficiency causes cardiac and forelimb abnormalities
seen in Holt-Oram syndrome. Tbx5 deficiency in homozygous mice (Tbx5(del/del))
decreased expression of multiple genes and caused severe hypoplasia
of posterior domains in the developing heart. Surprisingly, Tbx5
haploinsufficiency also markedly decreased atrial natriuretic factor
(ANF) and connexin 40 (cx40) transcription, implicating these as
Tbx5 target genes and providing a mechanism by which 50% reduction
of T-box transcription factors cause disease. Direct and cooperative
transactivation of the ANF and cx40 promoters by Tbx5 and the homeodomain
transcription factor Nkx2-5 was also demonstrated. These studies
provide one potential explanation for Holt-Oram syndrome conduction
system defects, suggest mechanisms for intrafamilial phenotypic variability,
and account for related cardiac malformations caused by other transcription
factor mutations.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Bruneau, B. G. and Nemer, G. and Schmitt, J. P. and Charron, F. and Robitaille, L. and Caron, S. and Conner, D. A. and Gessler, M. and Nemer, M. and Seidman, C. E. and Seidman, J. G.},
biburl = {https://www.bibsonomy.org/bibtex/2a6620354f8e62c90c28de9661ff21e12/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {052356dada9a19057443c24c40726f49},
intrahash = {a6620354f8e62c90c28de9661ff21e12},
issn = {0092-8674 (Print) 0092-8674 (Linking)},
journal = {Cell},
keywords = {Abnormalities, Acid Aging Alignment Animal Animals Atrial Base Binding Bone Cell Congenital/*genetics/physiopathology Connexins/genetics Data Defects, Development Development/genetics/*physiology Differentiation Disease Domain Electrocardiography Embryonic Factor/*genetics Fetal Forelimb/abnormalities Genetic Heart Heart/embryology Heterozygote Homology, Homozygote Humans Knockout Mice Models, Molecular Multiple/*genetics Myocardium/cytology Natriuretic Nucleic Promoter Proteins/deficiency/*genetics Rats Regions, Sequence Sheep Sites Syndrome T-Box and},
month = {Sep 21},
note = {Bruneau, B G Nemer, G Schmitt, J P Charron, F Robitaille, L Caron,
S Conner, D A Gessler, M Nemer, M Seidman, C E Seidman, J G S10 RR14792/RR/NCRR
NIH HHS/United States Research Support, Non-U.S. Gov't Research Support,
U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United
States Cell Cell. 2001 Sep 21;106(6):709-21.},
number = 6,
pages = {709-21},
shorttitle = {A murine model of Holt-Oram syndrome defines roles of the T-box transcription
factor Tbx5 in cardiogenesis and disease},
timestamp = {2010-12-14T18:21:24.000+0100},
title = {A murine model of Holt-Oram syndrome defines roles of the T-box transcription
factor Tbx5 in cardiogenesis and disease},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11572777},
volume = 106,
year = 2001
}