Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice.
Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development.
Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania.
John M
JM
Starbuck
Department of Physiology and Institute for Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Tara
T
Dutka
Department of Physiology and Institute for Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Tabetha S
TS
Ratliff
Department of Physiology and Institute for Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Roger H
RH
Reeves
Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania.|Center for Functional Anatomy and Evolution, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Joan T
JT
Richtsmeier
D000818:Animals; D001921:Brain / Q000473:pathology*; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051379:Mice; D010641:Phenotype; D012886:Skull / Q000473:pathology*
Down syndrome; brain morphology; craniofacial morphogenesis; gene-dosage imbalance; trisomy 21