Evaluation of endochondral skeletogenesis in the Ts65Dn mouse model for Down syndrome during embryonic development
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Down syndrome (DS) is a complex genetic disorder caused by the triplication of human chromosome 21. This disorder has been linked to numerous abnormalities affecting nearly every system in the body. Phenotypes pertaining to the appendicular skeleton, such as shorter humerus and femur lengths in DS fetuses, short stature and reduced bone mineral density have been identified, but very little is known regarding their etiology. Study concerning the developmental basis of such abnormal phenotypes will provide information regarding their origin in order to aid individuals with DS. The model organism to be used in this study is the Ts65Dn mouse model for DS in which comparable human DS skeletal phenotypes have been identified in adult mice. Based upon the previously described skeletal phenotypes, we expect to observe differences in the development of the cartilage anlagen in Ts65Dn embryos relative to their euploid littermates. My study examines embryonic day (E)13.5-14.5, a crucial timeframe in skeletal development when the cartilage anlagen of the limbs has formed and ossification has just begun. Various markers of skeletal development were examined using Alcian Blue and Alizarin Red S staining as well as immunohistology. The results of this study demonstrate that there was no significant difference in femur or humerus lengths between E13.5 Ts65Dn and euploid embryos. In addition, no obvious distinctions between the morphology of chondrocytes, their distribution within the cartilage anlagen or the expression of specific marker proteins (collagen X and collagen II) were observed between genotypes, although there was variable expression of collagen X among all embryos. While the findings presented in this study do not directly support existing phenotypes observed at later stages of murine development in the Ts65Dn model, they do not conflict with preexisting findings either. As the results of this study suggest that the formation of the cartilage anlagen is normal in Ts65Dn mice at E13.5-14.5, preliminary research has been conducted examining the next steps in endochondral ossification, cartilage matrix mineralization and angiogenesis. Evaluation of these processes may provide insight regarding the etiology of the abnormal appendicular skeletal phenotypes observed in adult Ts65Dn mice and individuals with DS.
Franklin and Marshall College Archives, Undergraduate Honors Thesis 2012
- F&M Theses Collection 
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Characterization of congenital vascular and intracardiac defects in the Ts65Dn murine model for Down syndrome Williams, Austin D. (2007)The Ts65Dn mouse is the most-studied murine model for Down syndrome (DS) or trisomy 21. Homology between triplicated murine genes and genes on human chromosome 21 (Hsa21) correlates with the shared anomalies of Ts65Dn ...
Branchial arch artery formation and apoptosis during cardiogenesis in the Ts65Dn mouse model for Down syndrome Hakkinen, Lauren A. (2007)Ts65Dn is the mouse model most widely used in Down syndrome (DS) research. In this model, triplication of the distal portion of mouse chromosome 16 (MMU16), which contains orthologs to genes on human chromosome 21, results ...
Quantification and analysis of apoptosis in embryonic atrioventricular endocardial cushions of the Ts65Dn mouse model for Down syndrome Gotlieb, Naomi R. (2009)The Ts65Dn mouse model for Down syndrome (DS) has triplication of more than half of the mouse genes orthologous to those on human chromosome 21, and exhibits many phenotypes characteristic of human DS. Previous gross ...