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Opposing phenotypes in mice with Smith–Magenis deletion and Potocki–Lupski duplication syndromes suggest gene dosage effects on fluid consumption behavior§

Authors

  • Detlef H. Heck,

    Corresponding author
    1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee
    • Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN.
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  • Wenli Gu,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Ying Cao,

    1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Shuhua Qi,

    1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Melanie Lacaria,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • James R. Lupski

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    3. Texas Children's Hospital, Houston, Texas
    • Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
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  • How to Cite this Article: Heck DH, Gu W, Cao Y, Qi S, Lacaria M, Lupski JR. 2012. Opposing phenotypes in mice with Smith–Magenis deletion and Potocki–Lupski duplication syndromes suggest gene dosage effects on fluid consumption behavior. Am J Med Genet Part A 158A: 2807–2814.

  • Conflict of Interest Statement: None declared.

  • §

    Disclosure: J.R.L. is a consultant for Athena Diagnostics, holds stock ownership in 23andMe and Ion Torrent Systems, and is a coinventor on multiple United States and European patents for DNA diagnostics. The Department of Molecular and Human Genetics at the Baylor College of Medicine derives revenue from clinical testing using genetic and genomic assays.

Abstract

A quantitative long-term fluid consumption and fluid-licking assay was performed in two mouse models with either an ∼2 Mb genomic deletion, Df(11)17, or the reciprocal duplication copy number variation (CNV), Dp(11)17, analogous to the human genomic rearrangements causing either Smith–Magenis syndrome [SMS; OMIM #182290] or Potocki–Lupski syndrome [PTLS; OMIM #610883], respectively. Both mouse strains display distinct quantitative alterations in fluid consumption compared to their wild-type littermates; several of these changes are diametrically opposing between the two chromosome engineered mouse models. Mice with duplication versus deletion showed longer versus shorter intervals between visits to the waterspout, generated more versus less licks per visit and had higher versus lower variability in the number of licks per lick-burst as compared to their respective wild-type littermates. These findings suggest that copy number variation can affect long-term fluid consumption behavior in mice. Other behavioral differences were unique for either the duplication or deletion mutants; the deletion CNV resulted in increased variability of the licking rhythm, and the duplication CNV resulted in a significant slowing of the licking rhythm. Our findings document a readily quantitated complex behavioral response that can be directly and reciprocally influenced by a gene dosage effect. © 2012 Wiley Periodicals, Inc.

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