down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes.
Abstract
Two mouse models are widely used for Down syndrome (DS) research. The Ts65Dn mouse carries a small chromosome derived primarily from mouse chromosome 16, causing dosage imbalance for approximately half of human chromosome 21 orthologs. These mice have cerebellar pathology with direct parallels to DS. The Ts1Cje mouse, containing a translocated chromosome 16, is at dosage imbalance for 67% of the genes triplicated in Ts65Dn. We quantified cerebellar volume and granule cell and Purkinje cell density in Ts1Cje. Cerebellar volume was significantly affected to the same degree in Ts1Cje and Ts65Dn, despite that Ts1Cje has fewer triplicated genes. However, dosage imbalance in Ts1Cje had little effect on granule cell and Purkinje cell density. Several mice with dosage imbalance for the segment of the Ts65Dn chromosome not triplicated in Ts1Cje had phenotypes that contrasted with those in Ts1Cje. These observations do not readily differentiate between two prevalent hypotheses for gene action in DS.
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Similar to human studies, neuronal hypocellularity has been detected in multiple structures including the cortex, cerebellum, and hippocampus in postnatal trisomic Ts65Dn animals.
“Similar to human studies, neuronal hypocellularity has been detected in multiple structures including the cortex, cerebellum, and hippocampus in postnatal trisomic animals (Insausti et al., 1998; Baxter et al., 2000; Olson et al., 2004; Roper et al., 2006; Chakrabarti et al., 2010; Aziz et al., 2018).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Olson et al., 2004
Unlike humans, this hypocellularity does not appear to be driving persistent volumetric changes in these structures, as size deficits detected prenatally do not persist postnatally except in the cerebellum.
“However, unlike humans, this hypocellularity does not appear to be driving persistent volumetric changes in these structures, as size deficits detected prenatally (Chakrabarti et al., 2007) do not persist postnatally except in the cerebellum (Baxter et al., 2000; Olson et al., 2004).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Olson et al., 2004
Cites
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Chromosome 21 and Down syndrome: from genomics to pathophysiology
Antonarakis, S. E., Lyle, R., Dermitzakis, E. T., Reymond, A., & Deutsch, S. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1448 · Cited by 703 · see citing works
Chakrabarti, L., Galdzicki, Z., & Haydar, T. F. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3406-07.2007 · Cited by 199 · see citing works
Communication breaks-Down: From neurodevelopment defects to cognitive disabilities in Down syndrome
Contestabile, A., Benfenati, F., & Gasparini, L. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.003 · Cited by 134 · see citing works
Kazuki, Y., Gao, F. J., Li, Y., Moyer, A. J., Devenney, B., Hiramatsu, K., Miyagawa-Tomita, S., Abe, S., Kazuki, K., Kajitani, N., et al. (2020) · eLife · doi:10.7554/elife.56223 · Cited by 125 · see citing works
Self-citationAziz, N. M., Guedj, F., Pennings, J. L. A., Olmos-Serrano, J. L., Siegel, A., Haydar, T. F., & Bianchi, D. W. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.031013 · Cited by 118 · see citing works
Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors
Meharena, H. S., Marco, A., Dileep, V., Lockshin, E. R., Akatsu, G. Y., Mullahoo, J., Watson, L. A., Ko, T., Guerin, L. N., Abdurrob, F., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2021.12.002 · Cited by 92 · see citing works
Neurodevelopment in Down syndrome: Concordance in humans and models
Klein, J. A., & Haydar, T. F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.941855 · Cited by 47 · see citing works
“, 2007) do not persist postnatally except in the cerebellum (Baxter et al., 2000; Olson et al., 2004).”
BackgroundResultShaw, P. R., Klein, J. A., Aziz, N. M., & Haydar, T. F. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.046243 · Cited by 45 · see citing works
- Authors
- Olson, L. E., Roper, R. J., Baxter, L. L., Carlson, E. J., Epstein, C. J., & Reeves, R. H.
- Affiliations
- Johns Hopkins University (US)
- University of California, San Francisco (US)
- Corresponding author
- Reeves, R.H.
- Venue
- Developmental Dynamics
- Publisher
- Wiley
- Published
- 2004-05-12
- Volume
- 230
- Issue
- 3
- Pages
- 581-589
- ISSN
- 1058-8388 (ISSN-L)
- 1097-0177
- OpenAlex
- W1989308975
- Cited by
- 165
- References
- 2
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 11 · 2013: 10 · 2012: 14
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Dynamics (publishedVersion)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health (5r01hd031498-05)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-31498, P01HD24605, HD-24605, 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, cerebellum, cerebellar volume, granule cells, Purkinje cells, gene dosage imbalance, mouse model
- MeSH terms
- Animals, Cerebellum, Crosses, Genetic, Disease Models, Animal, Down Syndrome, Female, Genetic Markers, Granulocytes, Humans, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Organ Size, Phenotype, Purkinje Cells, Protein Biosynthesis, Trisomy, Ultrasonography, Sequence Deletion, Imaging, Three-Dimensional, Mice
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