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Cited by 35Down syndrome and intellectual disability researchWilliams Syndrome ResearchGenetics and Neurodevelopmental Disorders

Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of down syndrome-related phenotypes.

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Lana-Elola, Eva, Cater, Heather, Watson-Scales, Sheona, Greenaway, Simon, Müller-Winkler, Jennifer, Gibbins, Dorota, Nemes, Mihaela, Slender, Amy +18 more·2021·Disease Models & Mechanisms
DOI 10.1242/dmm.049157PMC PMC8543064

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Abstract

Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, these dosage-sensitive causative genes remain unknown. Animal models enable identification of genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. In order to establish whether this model recapitulates DS phenotypes, we comprehensively phenotyped Dp1Tyb mice using 28 tests of different physiological systems and found that 468 out of 1800 parameters were significantly altered. We show that Dp1Tyb mice have wide-ranging DS-like phenotypes, including aberrant erythropoiesis and megakaryopoiesis, reduced bone density, craniofacial changes, altered cardiac function, a pre-diabetic state, and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for investigating complex DS phenotype-genotype relationships for this common disorder.

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  • Dp1Tyb/Dp(16)1Yey replicate some developmental and learning and memory deficits of DS.

    “These mouse models have quickly become popular models of DS and replicate some of the same developmental and learning and memory deficits as individuals with DS (Goodliffe et al., 2016; Pinto et al., 2020; Lana-Elola et al., 2021).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Lana-Elola et al., 2021

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Cited by

Sorted by citations

Authors
Lana-Elola, E., Cater, H., Watson-Scales, S., Greenaway, S., Müller-Winkler, J., Gibbins, D., Nemes, M., Slender, A., Hough, T., Keskivali-Bond, P., Scudamore, C. L., Herbert, E., Banks, G. T., Mobbs, H., Canonica, T., Tosh, J., Noy, S., Llorian, M., Nolan, P. M., Griffin, J. L., Good, M., Simon, M., Mallon, A.-M., Wells, S., Fisher, E. M. C., & Tybulewicz, V. L. J.
Affiliations
  • The Francis Crick Institute, London NW1 1AT, UK
  • Mary Lyon Centre at MRC Harwell (GB)
  • The Francis Crick Institute (GB)
  • University of Cambridge (GB)
  • Cardiff University (GB)
  • UCL Queen Square Institute of Neurology (GB)
Corresponding author
  • Fisher, Elizabeth M. C.
  • Tybulewicz, Victor L. J.
ORCID
Venue
Disease Models & Mechanisms
Publisher
The Company of Biologists
Published
2021-10-01
Volume
14
Issue
10
ISSN
  • 1754-8403 (ISSN-L)
  • 1754-8411
DOI
10.1242/dmm.049157
PMC
PMC8543064
OpenAlex
W3197233693
Cited by
35
References
8
Citations by year
2026: 6 · 2025: 8 · 2024: 5 · 2023: 9 · 2022: 7
FWCI
4.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Disease Models & Mechanisms (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
  • The Francis Crick Institute (cc-by)
Funders
  • Wellcome Trust (080174, FC001194, 098327, 098328)
  • Medical Research Council (U117527252, FC001194, MC_U142684171)
  • Cancer Research UK (FC001194)
  • Seventh Framework Programme (312325)
  • National Human Genome Research Institute (UM1HG006370)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Down syndrome, phenotypic characterization, dosage-sensitive genes, erythropoiesis, megakaryopoiesis, bone mineral density, craniofacial anomalies, cardiac function, prediabetes, cognitive impairment, memory, locomotion, hearing, sleep
MeSH terms
Anemia, Animals, Bone Development, Disease Models, Animal, Down Syndrome, Erythropoiesis, Gene Expression Regulation, Hearing, Heart Function Tests, Hippocampus, Locomotion, Memory, Mice, Inbred C57BL, Otitis Media, Phenotype, Prediabetic State, Respiration, Sleep, Spleen, Splenomegaly, Evoked Potentials, Auditory, Brain Stem, Amyloid beta-Peptides, Genes, Duplicate, Mice

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