Craniofacial morphology of a new mouse model of Down syndrome

Abstract

Down syndrome (DS) is a complex condition caused by triplication of human chromosome 21 (Hsa21). Several mouse models have been developed to study the genotypic and phenotypic outcomes of DS. The most extensively studied and used in DS research is Ts65Dn. More recently, the TcMAC21 ‐ a transchromosomic mouse strain with comparable gene dosage to Hsa21 ‐ was developed, and represents a more complete genetic mouse model of DS than Ts65Dn. While Ts65Dn has been the focus of several studies, relatively little is known about the craniofacial phenotype of TcMAC21 mice relative to the other DS mouse models. Here we conducted a quantitative study of the cranial morphology of TcMAC21 and Ts65Dn mice and their respective unaffected littermates. Comparative data comprised of three‐dimensional cranial measurements taken from micro‐computed tomography scans of the mouse models used in the study. Our results show that TcMAC21 exhibit similar patterns of craniofacial change to Ts65Dn, but are less severe in their DS‐related cranial manifestations than Ts65Dn. TcMAC21 also do not present with the broadening and general ‘globularity’ of the cranium, particularly the face, as seen in Ts65Dn. Since Ts65Dn and TcMAC21 carry similarly large but not the same numbers of genes at dosage imbalance, our findings reveal the complexity of potential gene interaction in the production of craniofacial phenotypes.