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Abnormal mineralization of the Ts65Dn Down syndrome mouse appendicular skeleton begins during embryonic development in a Dyrk1a-independent manner

Authors :
Benedict Miller Foundation
William and Lucille Hackman Scholars Program
Jérôme Lejeune Foundation
Franklin & Marshall College
Blzek, Joshua D.
Malik, Ahmed M.
Tischbein, Maeve
Arbones, Maria L.
Moore, Clara S.
Roper, Randall J.
Benedict Miller Foundation
William and Lucille Hackman Scholars Program
Jérôme Lejeune Foundation
Franklin & Marshall College
Blzek, Joshua D.
Malik, Ahmed M.
Tischbein, Maeve
Arbones, Maria L.
Moore, Clara S.
Roper, Randall J.
Publication Year :
2015

Abstract

© 2014 Elsevier Ireland Ltd. The relationship between gene dosage imbalance and phenotypes associated with Trisomy 21, including the etiology of abnormal bone phenotypes linked to Down syndrome (DS), is not well understood. The Ts65Dn mouse model for DS exhibits appendicular skeletal defects during adolescence and adulthood but the developmental and genetic origin of these phenotypes remains unclear. It is hypothesized that the postnatal Ts65Dn skeletal phenotype originates during embryonic development and results from an increased Dyrk1a gene copy number, a gene hypothesized to play a critical role in many DS phenotypes. Ts65Dn embryos exhibit a lower percent bone volume in the E17.5 femur when compared to euploid embryos. Concomitant with gene copy number, qPCR analysis revealed a ~1.5 fold increase in Dyrk1a transcript levels in the Ts65Dn E17.5 embryonic femur as compared to euploid. Returning Dyrk1a copy number to euploid levels in Ts65Dn, Dyrk1a+/- embryos did not correct the trisomic skeletal phenotype but did return Dyrk1a gene transcript levels to normal. The size and protein expression patterns of the cartilage template during embryonic bone development appear to be unaffected at E14.5 and E17.5 in trisomic embryos. Taken together, these data suggest that the dosage imbalance of genes other than Dyrk1a is involved in the development of the prenatal bone phenotype in Ts65Dn embryos.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1103423778
Document Type :
Electronic Resource