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Cited by 434Down syndrome and intellectual disability researchGenomic variations and chromosomal abnormalitiesGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

An Aneuploid Mouse Strain Carrying Human Chromosome 21 with down Syndrome Phenotypes.

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O'Doherty, Aideen, Ruf, Sandra, Mulligan, Claire, Hildreth, Victoria, Errington, Mick L., Cooke, Sam, Sesay, Abdul, Modino, Sonie +10 more·2005·Science
DOI 10.1126/science.1114535PMC PMC1378183
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Abstract

Aneuploidies are common chromosomal defects that result in growth and developmental deficits and high levels of lethality in humans. To gain insight into the biology of aneuploidies, we manipulated mouse embryonic stem cells and generated a trans-species aneuploid mouse line that stably transmits a freely segregating, almost complete human chromosome 21 (Hsa21). This “transchromosomic” mouse line, Tc1, is a model of trisomy 21, which manifests as Down syndrome (DS) in humans, and has phenotypic alterations in behavior, synaptic plasticity, cerebellar neuronal number, heart development, and mandible size that relate to human DS. Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneuploidies.

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  • The Tc1 model had roughly 50 non-functional protein coding genes on HSA21 and was subject to loss of the human chromosome over development, creating mosaic mice difficult to study.

    “However, due to its manner of creation, roughly 50 of the protein coding genes on HSA21 were non-functional and this model was found to be subject to loss of the human chromosome over development creating mosaic mice that were difficult to study (O’Doherty et al., 2005; Gribble et al., 2013).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as O’Doherty et al., 2005

    The 'Chromosome retention and gene expression' section reports that only a proportion of adult Tc1 cells retained Hsa21, supporting the description of mosaic mice. The 'Generating the Tc1 transchromosomic mouse strains' section describes two gaps in the chromosome but estimates that it contains about 92% of known Hsa21 genes; it does not establish that roughly 50 protein-coding genes were non-functional. Nor does the copy establish progressive chromosome loss during development or say that mosaicism made the mice difficult to study. Page numbers were not available in the supplied copy. (LLM, conf=0.87)

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References 40 · Cited by 434

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Authors
O'Doherty, A., Ruf, S., Mulligan, C., Hildreth, V., Errington, M. L., Cooke, S., Sesay, A., Modino, S., Vanes, L., Hernandez, D., Linehan, J. M., Sharpe, P. T., Brandner, S., Bliss, T. V. P., Henderson, D. J., Nizetic, D., Tybulewicz, V. L. J., & Fisher, E. M. C.
Affiliations
  • Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
  • Queen Mary University of London (GB)
Corresponding author
  • Tybulewicz, Victor L. J.
  • Fisher, Elizabeth M. C.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2005-09-23
Volume
309
Issue
5743
Pages
2033-2037
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.1114535
PMC
PMC1378183
OpenAlex
W2097323692
Cited by
434
References
40
Citations by year
2026: 6 · 2025: 10 · 2024: 15 · 2023: 9 · 2022: 18 · 2021: 17 · 2020: 16 · 2019: 21 · 2018: 15 · 2017: 17 · 2016: 20 · 2015: 17 · 2014: 17 · 2013: 20 · 2012: 40
FWCI
28.65
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • Wellcome Trust (076700)
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
chromosome 21, Down syndrome, aneuploidy, mouse embryonic stem cells, synaptic plasticity, heart development, mandible size, mouse model
MeSH terms
Aneuploidy, Animals, Behavior, Animal, Brain, Cell Count, Cell Line, Chimera, Chromosomes, Human, Pair 21, Disease Models, Animal, Down Syndrome, Embryo, Mammalian, Facial Bones, Female, Genetic Engineering, Genetic Markers, Heart Defects, Congenital, Hippocampus, Humans, Lymphocyte Activation, Male, Memory, Mice, Inbred Strains, Mice, Transgenic, Synaptic Transmission, Neurons, Phenotype, Skull, Stem Cells, T-Lymphocytes, Gene Expression, Long-Term Potentiation, Maze Learning, Oligonucleotide Array Sequence Analysis, Mice

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