Generation of the Sotos syndrome deletion in mice

Sanger Mouse Genetics Project, Anna M Migdalska, Louise van der Weyden, Ozama Ismail, Alistair G Rust, Mamunur Rashid, Jacqueline K White, Gabriela Sánchez-Andrade, James R Lupski, Darren W Logan, Mark J Arends, David J Adams

Research output: Contribution to journalArticlepeer-review

Abstract

Haploinsufficiency of the human 5q35 region spanning the NSD1 gene results in a rare genomic disorder known as Sotos syndrome (Sotos), with patients displaying a variety of clinical features, including pre- and postnatal overgrowth, intellectual disability, and urinary/renal abnormalities. We used chromosome engineering to generate a segmental monosomy, i.e., mice carrying a heterozygous 1.5-Mb deletion of 36 genes on mouse chromosome 13 (4732471D19Rik-B4galt7), syntenic with 5q35.2-q35.3 in humans (Df(13)Ms2Dja ( +/- ) mice). Surprisingly Df(13)Ms2Dja ( +/- ) mice were significantly smaller for their gestational age and also showed decreased postnatal growth, in contrast to Sotos patients. Df(13)Ms2Dja ( +/- ) mice did, however, display deficits in long-term memory retention and dilation of the pelvicalyceal system, which in part may model the learning difficulties and renal abnormalities observed in Sotos patients. Thus, haploinsufficiency of genes within the mouse 4732471D19Rik-B4galt7 deletion interval play important roles in growth, memory retention, and the development of the renal pelvicalyceal system.
Original languageEnglish
Pages (from-to)749-57
Number of pages9
JournalMammalian Genome
Volume23
Issue number11-12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Absorptiometry, Photon
  • Animals
  • Blotting, Southern
  • Body Weights and Measures
  • Chromosome Deletion
  • Chromosomes, Human, Pair 5
  • Comparative Genomic Hybridization
  • DNA Primers
  • Disease Models, Animal
  • Gene Targeting
  • Growth and Development
  • Haploinsufficiency
  • Histological Techniques
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kidney
  • Memory Disorders
  • Mice
  • Sotos Syndrome

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