A deficiency in the region homologous to human 17q21.33-q23.2 causes heart defects in mice
| Autor: | Y. Eugene Yu, Annie Pao, Xiao-Yan Wen, Antonio Baldini, Ding Yan Wang, Masae Morishima, Allan Bradley |
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| Přispěvatelé: | Y. E., Yu, M., Morishima, A., Pao, D. Y., Wang, X. Y., Wen, Baldini, Antonio, A., Bradley |
| Rok vydání: | 2006 |
| Předmět: |
Genetic Markers
Heart Defects Congenital Genotype Mutant Cardiovascular Abnormalities Biology Investigations Synteny Mice Gene Duplication Sequence Homology Nucleic Acid Genomic Segment Gene duplication Genetics Animals Humans Gene Fetal Death Homeodomain Proteins Recombination Genetic Genome Molecular biology Phenotype Chromosomes Mammalian Chromosome 17 (human) Survival Rate Homeobox Chromosome Deletion Chromosomes Human Pair 17 |
| Zdroj: | Genetics. 173(1) |
| ISSN: | 0016-6731 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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