Modeling partial monosomy for human chromosome 21q11.2-q21.1 reveals haploinsufficient genes influencing behavior and fat deposition

Sanger Mouse Genetics Project, Anna M Migdalska, Louise van der Weyden, Ozama Ismail, Jacqueline K White, Gabriela Sánchez-Andrade, Darren W Logan, Mark J Arends, David J Adams

Research output: Contribution to journalArticlepeer-review

Abstract

Haploinsufficiency of part of human chromosome 21 results in a rare condition known as Monosomy 21. This disease displays a variety of clinical phenotypes, including intellectual disability, craniofacial dysmorphology, skeletal and cardiac abnormalities, and respiratory complications. To search for dosage-sensitive genes involved in this disorder, we used chromosome engineering to generate a mouse model carrying a deletion of the Lipi-Usp25 interval, syntenic with 21q11.2-q21.1 in humans. Haploinsufficiency for the 6 genes in this interval resulted in no gross morphological defects and behavioral analysis performed using an open field test, a test of anxiety, and tests for social interaction were normal in monosomic mice. Monosomic mice did, however, display impaired memory retention compared to control animals. Moreover, when fed a high-fat diet (HFD) monosomic mice exhibited a significant increase in fat mass/fat percentage estimate compared with controls, severe fatty changes in their livers, and thickened subcutaneous fat. Thus, genes within the Lipi-Usp25 interval may participate in memory retention and in the regulation of fat deposition.
Original languageEnglish
Pages (from-to)e29681
JournalPLoS ONE
Volume7
Issue number1
DOIs
Publication statusPublished - 2012

Keywords / Materials (for Non-textual outputs)

  • Absorptiometry, Photon
  • Animals
  • Behavior, Animal
  • Blotting, Southern
  • Cell Line
  • Chromosome Deletion
  • Chromosomes, Human, Pair 21
  • Diet, High-Fat
  • Female
  • Haploinsufficiency
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Maze Learning
  • Mice
  • Monosomy
  • Recognition (Psychology)
  • Reverse Transcriptase Polymerase Chain Reaction

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