Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice

Joan T. Richtsmeier, Laura L. Baxter, Roger H Reeves

Research output: Contribution to journalArticle

Abstract

Mouse genetic models can be used to dissect molecular mechanisms that result in human disease. This approach requires detection and demonstration of compelling parallels between phenotypes in mouse and human. Ts65Dn mice are at dosage imbalance for many of the same genes duplicated in trisomy 21 or Down syndrome (DS), the most common live-born human aneuploidy. Analysis of the craniofacial skeleton of Ts65Dn mice using three-dimensional morphometric methods demonstrates an absolute correspondence between Ts65Dn and DS craniofacial dysmorphology, a distinctive and completely penetrant DS phenotype. The genes at dosage imbalance in Ts65Dn are localized to a small region of mouse chromosome 16 and, by comparative mapping, to the corresponding region of human Chromosome 21, providing independent experimental data supporting the contribution of genes in this region to this characteristic DS phenotype. This analysis establishes precise parallels in human and mouse skull phenotypes resulting from dosage imbalance for the same genes, revealing strong conservation of the evolved developmental genetic program that underlies mammalian skull morphology and validating the use of this mouse model in the analysis of this important DS phenotype. This evolutionary conservation further establishes the mouse as a valid model for a wide range of syndromes producing craniofacial maldevelopment.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalDevelopmental Dynamics
Volume217
Issue number2
DOIs
StatePublished - 2000

Fingerprint

Down Syndrome
Phenotype
Skull
Genes
Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 21
Gene Dosage
Genetic Models
Human Chromosomes
Aneuploidy
Skeleton

Keywords

  • Aneuploidy
  • Euclidean distance matrix analysis
  • Evolution
  • Morphometrics
  • Segmental trisomy
  • Skull development

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. / Richtsmeier, Joan T.; Baxter, Laura L.; Reeves, Roger H.

In: Developmental Dynamics, Vol. 217, No. 2, 2000, p. 137-145.

Research output: Contribution to journalArticle

Richtsmeier, Joan T. ; Baxter, Laura L. ; Reeves, Roger H. / Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. In: Developmental Dynamics. 2000 ; Vol. 217, No. 2. pp. 137-145.
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