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Cited by 78Down syndrome and intellectual disability researchGenetics and Neurodevelopmental DisordersWilliams Syndrome Research

Gene expression variation in Down's syndrome mice allows prioritization of candidate genes

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Sultan, Marc, Piccini, Ilaria, Balzereit, Daniela, Herwig, Ralf, Saran, Nidhi G, Lehrach, Hans, Reeves, Roger H, Yaspo, Marie-Laure·2007·Genome Biology
DOI 10.1186/gb-2007-8-5-r91PMC PMC1929163
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Abstract

Background: Down's syndrome (DS), or trisomy 21, is a complex developmental disorder that exhibits many clinical signs that vary in occurrence and severity among patients. The molecular mechanisms responsible for DS have thus far remained elusive. We argue here that normal variation in gene expression in the population contributes to the heterogeneous clinical picture of DS, and we estimated the amplitude of this variation in 50 mouse orthologs of chromosome 21 genes in brain regions of Ts65Dn (a mouse model of DS). We analyzed the RNAs of eight Ts65Dn and eight euploid mice by real-time polymerase chain reaction. Results: In pooled RNAs, we confirmed that trisomic/euploid gene expression ratios were close to 1.5. However, we observed that inter-individual gene expression levels spanned a broad range of values. We identified three categories of genes: genes with expression levels consistently higher in Ts65Dn than in euploids (9, 17, and 7 genes in cerebellum, cortex, and midbrain, respectively); genes whose expression levels partially overlap between the two groups (10, 9, and 14 genes); and genes with intermingled expression, which cannot be used to differentiate trisomics from euploids (12, 5 and 9 genes). Of the genes in the first category, App, Cbr1, and Mrps6 exhibited tight regulation in the three tissues and are therefore attractive candidates for further research. Conclusion: This is the first analysis addressing inter-individual gene expression levels as a function of trisomy. We propose a strategy allowing discrimination between candidates for the constant features of DS and those genes that may contribute to the partially penetrant signs of DS.

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  • Discordant outcomes between Dyrk1a RNA and protein expression in brain have been reported in older male Ts65Dn mice, although these comparisons came from different experiments.

    “Discordant outcomes between Dyrk1a RNA and protein expression in brain have been reported in older male Ts65Dn mice, although these comparisons came from different experiments (Ahmed et al., 2012; Choi et al., 2009; Sultan et al., 2007).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Sultan et al., 2007

    The Results section, “Expression of mmu21 genes in brain” (page not supplied), reports measuring brain transcripts in adult Ts65Dn mice and identifies Dyrk1a among the expressed genes. The Methods specify that the mice were male and 13–16 weeks old. The cited paper does not report Dyrk1a protein measurements or an RNA–protein discrepancy, so it supports only the RNA-study component of the comparison. (LLM, conf=0.83)

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Authors
Sultan, M., Piccini, I., Balzereit, D., Herwig, R., Saran, N. G., Lehrach, H., Reeves, R. H., & Yaspo, M.-L.
Affiliations
  • Max Planck Institute for Molecular Genetics (DE)
  • Johns Hopkins University (US)
Corresponding author
Sultan, Marc
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2007-05-25
Volume
8
Issue
5
Pages
R91-R91
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/gb-2007-8-5-r91
PMC
PMC1929163
OpenAlex
W2105642934
Cited by
78
References
38
Citations by year
2025: 1 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 8 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 1 · 2012: 4
FWCI
9.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
Funders
  • European Commission
  • Max-Planck-Gesellschaft
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD038384, R01HD038384)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
Keywords
Down syndrome, Ts65Dn mouse model, gene expression variation, brain gene expression, cerebellum, cerebral cortex, midbrain, APP, CBR1, candidate genes, phenotypic heterogeneity, penetrance
MeSH terms
Animals, Brain, Disease Models, Animal, Down Syndrome, Gene Expression Regulation, RNA, Trisomy, Genetic Variation, Mice

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