A mouse model for Down syndrome exhibits learning and behaviour deficits
Abstract
Trisomy 21 or Down syndrome (DS) is the most frequent genetic cause of mental retardation, affecting one in 800 live born human beings. Mice with segmental trisomy 16 (Ts65Dn mice) are at dosage imbalance for genes corresponding to those on human chromosome 21q21-22.3--which includes the so-called DS 'critical region'. They do not show early-onset of Alzheimer disease pathology; however, Ts65Dn mice do demonstrate impaired performance in a complex learning task requiring the integration of visual and spatial information. The reproducibility of this phenotype among Ts65Dn mice indicates that dosage imbalance for a gene or genes in this region contributes to this impairment. The corresponding dosage imbalance for the human homologues of these genes may contribute to cognitive deficits in DS.
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Ts65Dn and Ts1Cje mice survive to adulthood and exhibit morphological, biochemical, and transcriptional changes seen in human DS.
“Two segmental trisomy mouse models of DS, Ts65Dn (Davisson et al., 1990), and Ts1Cje (Sago et al., 1998) mice, survive to adulthood and exhibit a number of the morphological, biochemical, and transcriptional changes seen in the human disease (Davisson et al., 1990;Reeves et al., 1995;Holtzman et al., 1996).”
From <i>App</i>Gene Dosage Modulates Endosomal Abnormalities of Alzheimer's Disease in a Segmental Trisomy 16 Mouse Model of Down Syndrome (2003) · cites this paper as Reeves et al., 1995
Ts65Dn mice with a segmental trisomy extending from App to Mx1 exhibit behavioral and cognitive abnormalities not unlike some abnormalities seen in individuals with DS.
“Ts65Dn mice with a segmental trisomy extending from App to Mx1 exhibit behavioral and cognitive abnormalities not unlike some of the abnormalities seen in individuals with DS (Reeves et al., 1995).”
From <i>App</i>Gene Dosage Modulates Endosomal Abnormalities of Alzheimer's Disease in a Segmental Trisomy 16 Mouse Model of Down Syndrome (2003) · cites this paper as Reeves et al., 1995
The Ts65Dn DS mouse model offers a third copy of approximately half of the Hsa21 orthologs on a freely segregating extra marker chromosome.
“The Ts65Dn DS mouse model has been widely used and offers a third copy of approximately half of the Hsa21 orthologs on a freely segregating extra marker chromosome (Reeves et al., 1995).”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Reeves et al., 1995
Ts65Dn mice are one of many DS mouse models and have been the primary model used in DS preclinical neurobiological and neuro-behavioral research, including extensive use in testing therapies designed to normalize DS phenotypes.
“Ts65Dn mice are one of many DS mouse models and have been the primary model used in DS preclinical neurobiological and neuro-behavioral research, including extensive use in testing therapies designed to normalize DS phenotypes (Garcia-Cerro et al., 2017; Gardiner, 2015; Reeves et al., 1995).”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Reeves et al., 1995
Behaviorally, Ts65Dn appears to capture many of the features of Down syndrome including developmental delays and learning and memory deficits.
“Behaviorally, Ts65Dn appears to capture many of the features of DS including developmental delays and learning and memory deficits (Reeves et al., 1995; Olmos-Serrano et al., 2016b; Shaw et al., 2020).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Reeves et al., 1995
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“Female B6EiC3Sn a/A-Ts(17 16 )65Dn/J (Ts65Dn) mice (Jackson Laboratory stock number 001924) containing a small marker chromosome (trisomic) (Reeves et al., 1995) were crossed with B6C3F1 male mice (Jackson Laboratory stock number 100010), producing both wildtype (euploid) and trisomic offspring…”
- Authors
- Reeves, R. H., Irving, N. G., Moran, T. H., Wohn, A., Kitt, C., Sisodia, S. S., Schmidt, C., Bronson, R. T., & Davisson, M. T.
- Affiliations
- Johns Hopkins University (US)
- Jackson Laboratory (US)
- Venue
- Nature Genetics
- Published
- 1995-10
- Volume
- 11
- Issue
- 2
- Pages
- 177-184
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2084233122
- Cited by
- 913
- References
- 1
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 34 · 2023: 23 · 2022: 36 · 2021: 34 · 2020: 31 · 2019: 33 · 2018: 28 · 2017: 40 · 2016: 33 · 2015: 36 · 2014: 38 · 2013: 41 · 2012: 46
- FWCI
- 29.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hd013131-004, 2r01hg000405-07a1)
- National Human Genome Research Institute (HG 00405)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-24605, HD13131, P01HD024605)
- 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, mouse model, learning deficits, spatial learning, cognitive impairment, intellectual disability, dosage imbalance, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Analysis of Variance, Animals, Chromosome Mapping, Chromosomes, Human, Pair 21, Disease Models, Animal, Down Syndrome, Female, Humans, Learning, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Neurologic Mutants, Motor Activity, Sex Characteristics, Gene Expression, Amyloid beta-Peptides, Mice
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