Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region

Elizabeth A. Lindsay, Antonio Baldini

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Chromosome 22q11.2 heterozygous deletions cause the most common deletion syndrome, including the DiGeorge syndrome phenotype. Using a mouse model of this deletion (named Df1) we show that the aortic arch patterning defects that occur in heterozygously deleted mice (Df1/+) are associated with a differentiation impairment of vascular smooth muscle in the 4th pharyngeal arch arteries (PAAs) during early embryogenesis. Using molecular markers for neural crest, endothelial cells and vascular smooth muscle, we show that cardiac neural crest migration into the 4th arch and initial formation of the 4th PAAs are apparently normal in Df1/+ embryos, but affected vessels are growth-impaired and do not acquire vascular smooth muscle. As in humans, not all deleted mice present with cardiovascular defects at birth. However, we found, unexpectedly, that all Df1/+ embryos have abnormally small 4th PAAs during early embryogenesis. Many embryos later overcome this early defect, coincident with the appearance of vascular smooth muscle differentiation, and develop normally. Embryos born with aortic arch patterning defects probably represent a more severely affected group that fails to attain sufficient 4th PAA growth for normal remodelling of the PAA system. Our data indicate that Df1/+ embryos are able to overcome a localized arterial growth impairment and thereby reduce the penetrance of birth defects.

Original languageEnglish
Pages (from-to)997-1002
Number of pages6
JournalHuman Molecular Genetics
Volume10
Issue number9
Publication statusPublished - Apr 15 2001

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DiGeorge Syndrome
Branchial Region
Penetrance
Vascular Smooth Muscle
Embryonic Structures
Arteries
Growth
Neural Crest
Thoracic Aorta
Embryonic Development
Endothelial Cells
Chromosomes
Phenotype

ASJC Scopus subject areas

  • Genetics

Cite this

Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region. / Lindsay, Elizabeth A.; Baldini, Antonio.

In: Human Molecular Genetics, Vol. 10, No. 9, 15.04.2001, p. 997-1002.

Research output: Contribution to journalArticle

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