RGD Reference Report - The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in telencephalic midline. - Rat Genome Database
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The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in telencephalic midline.

Authors: Jiang, X  Zhou, Y  Xian, L  Chen, W  Wu, H  Gao, X 
Citation: Jiang X, etal., Am J Pathol. 2012 Aug;181(2):626-41. doi: 10.1016/j.ajpath.2012.05.006. Epub 2012 May 29.
RGD ID: 9068442
Pubmed: (View Article at PubMed) PMID:22658483
DOI: Full-text: DOI:10.1016/j.ajpath.2012.05.006

Mutations in chromosome-helicase-DNA-binding protein 7 (CHD7) are identified as the main cause for CHARGE syndrome (coloboma, heart anomaly, choanal atresia, retardation, genital and ear anomalies). Most patients (55% to 85%) with CHARGE syndrome display developmental defects in the central nervous system (CNS), of which pathology and molecular mechanisms remain unclear. In this study, we report a novel mutant mouse strain carrying a nonsense mutation, COA1, in exon4 of Chd7 gene. Chd7(COA1/+) mice phenocopied human CHARGE syndrome and displayed developmental defects in the telencephalic midline, including dilated third and lateral ventricles, reduced cerebral cortex, and corpus callosum crossing failure. Programed cell death in the telencephalic midline zone of Chd7(COA1/+) embryos was impaired, consistent with the incomplete telencephalic medial invagination in Chd7(COA1/+) embryos. Interestingly, expression of Bmp4, a signal well known to induce forebrain midline cell fate and apoptosis, was down-regulated and also expanded in the forebrain of Chd7(COA1/+) embryos. Furthermore, in vitro studies suggested that CHD7 may directly regulate Bmp4 expression by binding with an enhancer element downstream of the Bmp4 locus. These studies provide novel insight into pathogenesis of CNS anomalies in CHARGE syndrome.


Disease Annotations    
CHARGE syndrome  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Bmp4  (bone morphogenetic protein 4)

Genes (Mus musculus)
Bmp4  (bone morphogenetic protein 4)

Genes (Homo sapiens)
BMP4  (bone morphogenetic protein 4)

Additional Information