Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies
Open Access
- 19 May 2005
- journal article
- research article
- Published by Wiley in Developmental Dynamics
- Vol. 233 (3) , 954-963
- https://doi.org/10.1002/dvdy.20433
Abstract
The Down syndrome critical region 1 (DSCR1) gene is located in syntenic regions of human chromosome 21 and mouse chromosome 16 and encodes a regulatory protein in the calcineurin/NFAT pathway. DSCR1 expression in the embryonic brain, craniofacial structures, and heart is consistent with a role in contributing to Down syndrome developmental anomalies. In the trisomy 16 (Ts16) murine model of Down syndrome, expression of DSCR1 isoforms is elevated and NFAT transcriptional activity is decreased in the developing heart and brain. The individual contribution of DSCR1 to Down syndrome‐related anomalies was examined by specific restoration of DSCR1 to disomic levels in Ts16 embryos. However, genetic restoration of DSCR1 did not rescue major morphological abnormalities in cardiac or craniofacial development. These data demonstrate that trisomy of DSCR1 alone does not significantly contribute to developmental defects in Ts16 mice and underscore the complexity of developmental anomalies associated with Down syndrome. Developmental Dynamics 233:954–963, 2005.Keywords
This publication has 43 references indexed in Scilit:
- The Drosophila homolog of Down's syndrome critical region 1 gene regulates learning: Implications for mental retardationProceedings of the National Academy of Sciences, 2003
- The DSCR1 ( Adapt78 ) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium‐mediated stress damage, including transient oxidative stressThe FASEB Journal, 2002
- Chronic Overexpression of the Calcineurin Inhibitory Gene DSCR1 (Adapt78)Is Associated with Alzheimer's DiseasePublished by Elsevier ,2001
- Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressed in the primitive ventricle of the heart and during neurogenesisMechanisms of Development, 2001
- The DNA sequence of human chromosome 21Nature, 2000
- The embryonic development of sensory organs and the skull in the trisomy 16 mouse, an animal model for Down's syndromeAnnals of Anatomy - Anatomischer Anzeiger, 1997
- Genomic Organization, Alternative Splicing, and Expression Patterns of theDSCR1(Down Syndrome Candidate Region 1) GeneGenomics, 1997
- Morphogenetic alterations during endocardial cushion development in the trisomy 16 (Down syndrome) mousePediatric Cardiology, 1996
- A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heartHuman Molecular Genetics, 1995
- Mouse Trisomy 16: An Animal Model of Human Trisomy 21 (Down Syndrome)aAnnals of the New York Academy of Sciences, 1985