Transchromosomic cell model of Down syndrome shows aberrant migration, adhesion and proteome response to extracellular matrix.
BACKGROUND
Down syndrome (DS), caused by trisomy of human chromosome 21 (HSA21), is the most common genetic birth defect. Congenital heart defects (CHD) are seen in 40% of DS children, and >50% of all atrioventricular canal defects in infancy are caused by trisomy 21, but the causative genes remain unknown.


RESULTS
Here we show that aberrant adhesion and proliferation of DS cells can be reproduced using a transchromosomic model of DS (mouse fibroblasts bearing supernumerary HSA21). We also demonstrate a deacrease of cell migration in transchromosomic cells independently of their adhesion properties. We show that cell-autonomous proteome response to the presence of Collagen VI in extracellular matrix is strongly affected by trisomy 21.


CONCLUSIONS
This set of experiments establishes a new model system for genetic dissection of the specific HSA21 gene-overdose contributions to aberrant cell migration, adhesion, proliferation and specific proteome response to collagen VI, cellular phenotypes linked to the pathogenesis of CHD.
Delom
Frédéric
F
Queen Mary University of London, Institute of Cell and Molecular Science, UK. f.delom@qmul.ac.uk
Burt
Emma
E
Hoischen
Alex
A
Veltman
Joris
J
Groet
Jürgen
J
Cotter
Finbarr E
FE
Nizetic
Dean
D