Congenital heart disease in mice deficient for the DiGeorge syndrome region
- 1 September 1999
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 401 (6751) , 379-383
- https://doi.org/10.1038/43900
Abstract
The heterozygous chromosome deletion within the band 22q11 (del22q11) is an important cause of congenital cardiovascular defects1. It is the genetic basis of DiGeorge syndrome and causes the most common deletion syndrome in humans2. Because the deleted region is largely conserved in the mouse, we were able to engineer a chromosome deletion (Df1) spanning a segment of the murine region homologous to the human deleted region. Here we describe heterozygously deleted (Df1/+) mice with cardiovascular abnormalities of the same type as those associated with del22q11; we have traced the embryological origin of these abnormalities to defective development of the fourth pharyngeal arch arteries. Genetic complementation of the deletion using a chromosome duplicated for the Df1 DNA segment corrects the heart defects, indicating that they are caused by reduced dosage of genes located within Df1. The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. These mutants represent a mouse model of a human deletion syndrome generated by chromosome engineering.Keywords
This publication has 21 references indexed in Scilit:
- A Molecular Pathway Revealing a Genetic Basis for Human Cardiac and Craniofacial DefectsScience, 1999
- Congenital heart defects and 22q11 deletions: which genes count?Molecular Medicine Today, 1998
- Cloning and Comparative Mapping of the DiGeorge Syndrome Critical Region in the MouseGenomics, 1998
- ES2, a gene deleted in DiGeorge syndrome, encodes a nuclear protein and is expressed during early mouse development, where it shares an expression domain with a Goosecoid-like geneHuman Molecular Genetics, 1998
- Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organizationProceedings of the National Academy of Sciences, 1997
- Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and differential degree of gene conservationMammalian Genome, 1997
- Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.Journal of Medical Genetics, 1997
- UFD1L, a Developmentally Expressed Ubiquitination Gene, is Deleted in CATCH 22 SyndromeHuman Molecular Genetics, 1997
- A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region.Genome Research, 1997
- Chromosome engineering in miceNature, 1995