Craniofacial growth and development in a mouse model of Down syndrome

Abstract

Down syndrome (DS) is a developmental disorder caused by trisomy of human chromosome 21. Ts65Dn, a widely used mouse model of DS, has facilitated the study of mechanisms underlying the genotypic and phenotypic anomalies associated with DS. Previous studies have shown the adult cranium and brain to be markedly smaller in size in Ts65Dn mice relative to their euploid littermates. To determine how postnatal developmental patterns contribute to cranial variation in trisomic mice, we quantitatively compared growth trajectories from birth (postnatal day 0, P0) to postnatal day 6 (P6) in Ts65Dn and euploid mice. We hypothesized that trisomy affects cranial growth rate in Ts65Dn mice, causing size and shape differences between Ts65Dn and euploid mice. Multivariate regression and principal components analyses of craniofacial shape and size show some subtle differences between the trisomic and euploid mice at P0, but by P6 the trisomic mice are considerably smaller than the euploids. Interestingly, Ts65Dn at P6 are closer in both size and shape to P0 euploid mice than to euploid mice at P6 or newborn Ts65Dn. This could occur through changes in growth rate of Ts65Dn mice, resulting in the trisomic P6 mice retaining features common to younger, typically developing mice. Further research focusing on prenatal ages will provide a better understanding of how differences in timing of developmental events, such as delays in migration and mitosis of cranial neural crest cells in mouse model of DS, contribute to trisomic craniofacial growth and development.Support or Funding InformationR01‐HD038384 (RHR)