Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: Phenotypic consequences of gene dosage imbalance

Katherina Walz, Sandra Caratini-Rivera, Weimin Bi, Patricia Fonseca, Dena L. Mansouri, Jennifer Lynch, Hannes Vogel, Jeffrey L. Noebels, Allan Bradley, James R. Lupski

Research output: Contribution to journalArticle

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Abstract

Contiguous gene syndromes (CGS) are a group of disorders associated with chromosomal rearrangements of which the phenotype is thought to result from altered copy numbers of physically linked dosage-sensitive genes. Smith-Magenis syndrome (SMS) is a CGS associated with a deletion within band p11.2 of chromosome 17. Recently, patients harboring the predicted reciprocal duplication product [dup(17)(p11.2p11.2)] have been described as having a relatively mild phenotype. By chromosomal engineering, we created rearranged chromosomes carrying the deletion [Df(11)17] or duplication [Dp(11)17] of the syntenic region on mouse chromosome 11 that spans the genomic interval commonly deleted in SMS patients. Df(11)17/+ mice exhibit craniofacial abnormalities, seizures, marked obesity, and male-specific reduced fertility. Dp(11)17/+ animals are underweight and do not have seizures, craniofacial abnormalities, or reduced fertility. Examination of Df(11)17/Dp(11)17 animals suggests that most of the observed phenotypes result from gene dosage effects. Our murine models represent a powerful tool to analyze the consequences of gene dosage imbalance in this genomic interval and to investigate the molecular genetic bases of both SMS and dup(17)(p11.2p11.2).

Original languageEnglish
Pages (from-to)3646-3655
Number of pages10
JournalMolecular and Cellular Biology
Volume23
Issue number10
DOIs
StatePublished - May 1 2003
Externally publishedYes

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Smith-Magenis Syndrome
Gene Dosage
Craniofacial Abnormalities
Chromosomes
Phenotype
Fertility
Seizures
Genes
Chromosome Deletion
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 17
Thinness
Molecular Biology
Obesity

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice : Phenotypic consequences of gene dosage imbalance. / Walz, Katherina; Caratini-Rivera, Sandra; Bi, Weimin; Fonseca, Patricia; Mansouri, Dena L.; Lynch, Jennifer; Vogel, Hannes; Noebels, Jeffrey L.; Bradley, Allan; Lupski, James R.

In: Molecular and Cellular Biology, Vol. 23, No. 10, 01.05.2003, p. 3646-3655.

Research output: Contribution to journalArticle

Walz, Katherina ; Caratini-Rivera, Sandra ; Bi, Weimin ; Fonseca, Patricia ; Mansouri, Dena L. ; Lynch, Jennifer ; Vogel, Hannes ; Noebels, Jeffrey L. ; Bradley, Allan ; Lupski, James R. / Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice : Phenotypic consequences of gene dosage imbalance. In: Molecular and Cellular Biology. 2003 ; Vol. 23, No. 10. pp. 3646-3655.
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