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Cited by 24Down syndrome and intellectual disability researchGenomic variations and chromosomal abnormalitiesGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Mouse models of aneuploidy to understand chromosome disorders

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Tosh, Justin, Tybulewicz, Victor, Fisher, Elizabeth M. C.·2022·Mammalian Genome
DOI 10.1007/s00335-021-09930-zPMC PMC8913467
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Abstract

An organism or cell carrying a number of chromosomes that is not a multiple of the haploid count is in a state of aneuploidy. This condition results in significant changes in the level of expression of genes that are gained or lost from the aneuploid chromosome(s) and most cases in humans are not compatible with life. However, a few aneuploidies can lead to live births, typically associated with deleterious phenotypes. We do not understand why phenotypes arise from aneuploid syndromes in humans. Animal models have the potential to provide great insight, but less than a handful of mouse models of aneuploidy have been made, and no ideal system exists in which to study the effects of aneuploidy per se versus those of raised gene dosage. Here, we give an overview of human aneuploid syndromes, the effects on physiology of having an altered number of chromosomes and we present the currently available mouse models of aneuploidy, focusing on models of trisomy 21 (which causes Down syndrome) because this is the most common, and therefore, the most studied autosomal aneuploidy. Finally, we discuss the potential role of carrying an extra chromosome on aneuploid phenotypes, independent of changes in gene dosage, and methods by which this could be investigated further.

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  • Mouse models have allowed advances in deciphering mechanisms governing brain development and function and the consequences of Down syndrome-related manipulations.

    “These models have allowed the scientific community to make incredible advances in deciphering the mechanisms governing brain development and function, as well as the consequences of DS-related manipulations for those mechanisms18–22.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [21]

    The “Current mammalian models of aneuploidy” section (page unavailable) describes how Down syndrome mouse models reveal effects of gene-dosage manipulations on behaviour and cognition, supporting the brain-function portion of the claim. Our copy does not show that these models have deciphered mechanisms governing brain development; it also notes that existing models cannot isolate the effects of aneuploidy itself from gene dosage. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Tosh, J., Tybulewicz, V., & Fisher, E. M. C.
Affiliations
  • The Francis Crick Institute (GB)
  • UCL Queen Square Institute of Neurology (GB)
Corresponding author
Fisher, Elizabeth M. C.
ORCID
Venue
Mammalian Genome
Publisher
Springer Science and Business Media LLC
Published
2021-11-01
Volume
33
Issue
1
Pages
157-168
ISSN
  • 0938-8990 (ISSN-L)
  • 1432-1777
DOI
10.1007/s00335-021-09930-z
PMC
PMC8913467
OpenAlex
W3210261625
Cited by
24
References
3
Citations by year
2026: 2 · 2025: 2 · 2024: 11 · 2023: 5 · 2022: 4
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Mammalian Genome (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • wellcome trust (098328, 098327, FC001194)
  • medical research council (U117527252, FC001194)
  • cancer research uk (FC001194)
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
aneuploidy, Down syndrome, gene dosage, chromosome number, autosomal aneuploidy
MeSH terms
Aneuploidy, Animals, Chromosomes, Disease Models, Animal, Down Syndrome, Trisomy, Chromosome Disorders, Mice

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