A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice

Y. Eugene Yu, Masae Morishima, Annie Pao, Ding Yan Wang, Xiao Yan Wen, Antonio Baldini, Allan Bradley

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Several constitutional chromosomal rearrangements occur on human chromosome 17. Patients who carry constitutional deletions of 17q21.3-q24 exhibit distinct phenotypic features. Within the deletion interval, there is a genomic segment that is bounded by the myeloperoxidase and homeobox B1 genes. This genomic segment is syntenically conserved on mouse chromosome 11 and is bounded by the mouse homologs of the same genes (Mpo and HoxB1). To attain functional information about this syntenic segment in mice, we have generated a 6.9-Mb deletion [Df(11)18], the reciprocal duplication [Dp(11)18] between Mpo and Chad (the chondroadherin gene), and a 1.8-Mb deletion between Chad and HoxB1. Phenotypic analyses of the mutant mouse lines showed that the Dp(11)18/Dp(11)18 genotype was responsible for embryonic or adolescent lethality, whereas the Df(11)18/+ genotype was responsible for heart defects. The cardiovascular phenotype of the Df(11)18/+ fetuses was similar to those of patients who carried the deletions of 17q21.3-q24. Since heart defects were not detectable in Df(11)18/Dp(11)18 mice, the haplo-insufficiency of one or more genes located between Mpo and Chad may be responsible for the abnormal cardiovascular phenotype. Therefore, we have identified a new dosage-sensitive genomic region that may be critical for normal heart development in both mice and humans.

Original languageEnglish
Pages (from-to)297-307
Number of pages11
JournalGenetics
Volume173
Issue number1
DOIs
Publication statusPublished - May 2006

Fingerprint

Chad
Genotype
Genes
Phenotype
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 17
Homeobox Genes
Human Chromosomes
Peroxidase
Fetus

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Yu, Y. E., Morishima, M., Pao, A., Wang, D. Y., Wen, X. Y., Baldini, A., & Bradley, A. (2006). A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice. Genetics, 173(1), 297-307. https://doi.org/10.1534/genetics.105.054833

A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice. / Yu, Y. Eugene; Morishima, Masae; Pao, Annie; Wang, Ding Yan; Wen, Xiao Yan; Baldini, Antonio; Bradley, Allan.

In: Genetics, Vol. 173, No. 1, 05.2006, p. 297-307.

Research output: Contribution to journalArticle

Yu, YE, Morishima, M, Pao, A, Wang, DY, Wen, XY, Baldini, A & Bradley, A 2006, 'A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice', Genetics, vol. 173, no. 1, pp. 297-307. https://doi.org/10.1534/genetics.105.054833
Yu, Y. Eugene ; Morishima, Masae ; Pao, Annie ; Wang, Ding Yan ; Wen, Xiao Yan ; Baldini, Antonio ; Bradley, Allan. / A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice. In: Genetics. 2006 ; Vol. 173, No. 1. pp. 297-307.
@article{36ef36ddc56d4c3085e48bf7fd4e54d8,
title = "A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice",
abstract = "Several constitutional chromosomal rearrangements occur on human chromosome 17. Patients who carry constitutional deletions of 17q21.3-q24 exhibit distinct phenotypic features. Within the deletion interval, there is a genomic segment that is bounded by the myeloperoxidase and homeobox B1 genes. This genomic segment is syntenically conserved on mouse chromosome 11 and is bounded by the mouse homologs of the same genes (Mpo and HoxB1). To attain functional information about this syntenic segment in mice, we have generated a 6.9-Mb deletion [Df(11)18], the reciprocal duplication [Dp(11)18] between Mpo and Chad (the chondroadherin gene), and a 1.8-Mb deletion between Chad and HoxB1. Phenotypic analyses of the mutant mouse lines showed that the Dp(11)18/Dp(11)18 genotype was responsible for embryonic or adolescent lethality, whereas the Df(11)18/+ genotype was responsible for heart defects. The cardiovascular phenotype of the Df(11)18/+ fetuses was similar to those of patients who carried the deletions of 17q21.3-q24. Since heart defects were not detectable in Df(11)18/Dp(11)18 mice, the haplo-insufficiency of one or more genes located between Mpo and Chad may be responsible for the abnormal cardiovascular phenotype. Therefore, we have identified a new dosage-sensitive genomic region that may be critical for normal heart development in both mice and humans.",
author = "Yu, {Y. Eugene} and Masae Morishima and Annie Pao and Wang, {Ding Yan} and Wen, {Xiao Yan} and Antonio Baldini and Allan Bradley",
year = "2006",
month = "5",
doi = "10.1534/genetics.105.054833",
language = "English",
volume = "173",
pages = "297--307",
journal = "Genetics",
issn = "0016-6731",
publisher = "Genetics Society of America",
number = "1",

}

TY - JOUR

T1 - A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice

AU - Yu, Y. Eugene

AU - Morishima, Masae

AU - Pao, Annie

AU - Wang, Ding Yan

AU - Wen, Xiao Yan

AU - Baldini, Antonio

AU - Bradley, Allan

PY - 2006/5

Y1 - 2006/5

N2 - Several constitutional chromosomal rearrangements occur on human chromosome 17. Patients who carry constitutional deletions of 17q21.3-q24 exhibit distinct phenotypic features. Within the deletion interval, there is a genomic segment that is bounded by the myeloperoxidase and homeobox B1 genes. This genomic segment is syntenically conserved on mouse chromosome 11 and is bounded by the mouse homologs of the same genes (Mpo and HoxB1). To attain functional information about this syntenic segment in mice, we have generated a 6.9-Mb deletion [Df(11)18], the reciprocal duplication [Dp(11)18] between Mpo and Chad (the chondroadherin gene), and a 1.8-Mb deletion between Chad and HoxB1. Phenotypic analyses of the mutant mouse lines showed that the Dp(11)18/Dp(11)18 genotype was responsible for embryonic or adolescent lethality, whereas the Df(11)18/+ genotype was responsible for heart defects. The cardiovascular phenotype of the Df(11)18/+ fetuses was similar to those of patients who carried the deletions of 17q21.3-q24. Since heart defects were not detectable in Df(11)18/Dp(11)18 mice, the haplo-insufficiency of one or more genes located between Mpo and Chad may be responsible for the abnormal cardiovascular phenotype. Therefore, we have identified a new dosage-sensitive genomic region that may be critical for normal heart development in both mice and humans.

AB - Several constitutional chromosomal rearrangements occur on human chromosome 17. Patients who carry constitutional deletions of 17q21.3-q24 exhibit distinct phenotypic features. Within the deletion interval, there is a genomic segment that is bounded by the myeloperoxidase and homeobox B1 genes. This genomic segment is syntenically conserved on mouse chromosome 11 and is bounded by the mouse homologs of the same genes (Mpo and HoxB1). To attain functional information about this syntenic segment in mice, we have generated a 6.9-Mb deletion [Df(11)18], the reciprocal duplication [Dp(11)18] between Mpo and Chad (the chondroadherin gene), and a 1.8-Mb deletion between Chad and HoxB1. Phenotypic analyses of the mutant mouse lines showed that the Dp(11)18/Dp(11)18 genotype was responsible for embryonic or adolescent lethality, whereas the Df(11)18/+ genotype was responsible for heart defects. The cardiovascular phenotype of the Df(11)18/+ fetuses was similar to those of patients who carried the deletions of 17q21.3-q24. Since heart defects were not detectable in Df(11)18/Dp(11)18 mice, the haplo-insufficiency of one or more genes located between Mpo and Chad may be responsible for the abnormal cardiovascular phenotype. Therefore, we have identified a new dosage-sensitive genomic region that may be critical for normal heart development in both mice and humans.

UR - http://www.scopus.com/inward/record.url?scp=33744457328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744457328&partnerID=8YFLogxK

U2 - 10.1534/genetics.105.054833

DO - 10.1534/genetics.105.054833

M3 - Article

C2 - 16489219

AN - SCOPUS:33744457328

VL - 173

SP - 297

EP - 307

JO - Genetics

JF - Genetics

SN - 0016-6731

IS - 1

ER -