Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic "Down syndrome" mice

Cheryl A. Hill, Thomas E. Sussan, Roger H. Reeves, Joan Therese Richtsmeier

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Ts65Dn mice have segmental trisomy for orthologs of about half of the genes on human chromosome 21, including Ets2. These mice develop anomalies of the cranial skeleton and thymus that parallel those in Down syndrome. Overexpression of the Ets2 transcription factor gene was posited to be sufficient to produce these craniofacial and thymus deficits in transgenic mice that constitutively overexpress a processed Ets2 transcript under a promiscuous promoter [Sumarsono et al. (1996); Nature 379:534-537; Wolvetang et al. (2003); Hum Mol Genet 12:247-255]. Evaluation of trisomic mice with varying copy numbers of a properly regulated Ets2 gene indicated increased dosage of Ets2 was not sufficient to produce effects on thymus and most of the cranial anomalies seen in Ts65Dn mice. However, mesoderm-derived cranial skeletal elements are significantly more affected in Ts65Dn, Ets2+/- mice compared to Ts65Dn littermates suggesting a differential interaction of Ets2-related processes with mesoderm-derived and neural crest-derived formative tissues. Our results support the growing evidence for interactions among multiple genes contributing to developmental perturbations resulting in variation in complex Down syndrome phenotypes.

Original languageEnglish (US)
Pages (from-to)2158-2165
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Volume149
Issue number10
DOIs
StatePublished - Oct 1 2009

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Down Syndrome
Thymus Gland
Phenotype
Mesoderm
Genes
Viverridae
Chromosomes, Human, Pair 21
Neural Crest
Trisomy
Human Chromosomes
Skeleton
Transgenic Mice
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics

Cite this

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title = "Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic {"}Down syndrome{"} mice",
abstract = "Ts65Dn mice have segmental trisomy for orthologs of about half of the genes on human chromosome 21, including Ets2. These mice develop anomalies of the cranial skeleton and thymus that parallel those in Down syndrome. Overexpression of the Ets2 transcription factor gene was posited to be sufficient to produce these craniofacial and thymus deficits in transgenic mice that constitutively overexpress a processed Ets2 transcript under a promiscuous promoter [Sumarsono et al. (1996); Nature 379:534-537; Wolvetang et al. (2003); Hum Mol Genet 12:247-255]. Evaluation of trisomic mice with varying copy numbers of a properly regulated Ets2 gene indicated increased dosage of Ets2 was not sufficient to produce effects on thymus and most of the cranial anomalies seen in Ts65Dn mice. However, mesoderm-derived cranial skeletal elements are significantly more affected in Ts65Dn, Ets2+/- mice compared to Ts65Dn littermates suggesting a differential interaction of Ets2-related processes with mesoderm-derived and neural crest-derived formative tissues. Our results support the growing evidence for interactions among multiple genes contributing to developmental perturbations resulting in variation in complex Down syndrome phenotypes.",
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Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic "Down syndrome" mice. / Hill, Cheryl A.; Sussan, Thomas E.; Reeves, Roger H.; Richtsmeier, Joan Therese.

In: American Journal of Medical Genetics, Part A, Vol. 149, No. 10, 01.10.2009, p. 2158-2165.

Research output: Contribution to journalArticle

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