Molecular characterization of the translocation breakpoints in the down syndrome mouse model Ts65Dn
Open accessAbstract
Ts65Dn is a mouse model of Down syndrome: a syndrome that results from chromosome (Chr) 21 trisomy and is associated with congenital defects, cognitive impairment, and ultimately Alzheimer's disease. Ts65Dn mice have segmental trisomy for distal mouse Chr 16, a region sharing conserved synteny with human Chr 21. As a result, this strain harbors three copies of over half of the human Chr 21 orthologs. The trisomic segment of Chr 16 is present as a translocation chromosome (Mmu17(16)), with breakpoints that have not been defined previously. To molecularly characterize the Chrs 16 and 17 breakpoints on the translocation chromosome in Ts65Dn mice, we used a selective enrichment and high-throughput paired-end sequencing approach. Analysis of paired-end reads flanking the Chr 16, Chr 17 junction on Mmu17(16) and de novo assembly of the reads directly spanning the junction provided the precise locations of the Chrs 16 and 17 breakpoints at 84,351,351 and 9,426,822 bp, respectively. These data provide the basis for low-cost, highly efficient genotyping of Ts65Dn mice. More importantly, these data provide, for the first time, complete characterization of gene dosage in Ts65Dn mice.
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The most notable identified limitation of the Ts65Dn model is that the trisomic mice also contain ~35 protein coding genes found on mouse chromosome 17 that are not homologous to Hsa21.
“Limitations of the Ts65Dn model have been identified, the most notable being that the trisomic mice also contain ~35 protein coding genes found on mouse chromosome 17 that are not homologous to Hsa21 (Duchon et al., 2011; Reinholdt et al., 2011).”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Reinholdt et al., 2011
The Results (page unavailable) show that the extra Ts65Dn chromosome carries a mouse Chr 17 region syntenic with human Chr 6 rather than Hsa21. But the paper counts 60 annotations across protein-coding genes, pseudogenes, and non-coding RNAs; it does not establish the claimed figure of approximately 35 protein-coding genes. The Discussion (page unavailable) notes that the phenotypic effects of extra copies of genes in this region remain unknown. (LLM, conf=0.86)
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References 20 · Cited by 186
Research works printed but not linked: 18
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- Authors
- Reinholdt, L. G., Ding, Y., Gilbert, G. T., Czechanski, A., Solzak, J. P., Roper, R. J., Johnson, M. T., Donahue, L. R., Lutz, C., & Davisson, M. T.
- Affiliations
- Jackson Laboratory (US)
- Regeneron (United States) (US)
- Purdue University in Indianapolis (US)
- University of Michigan (US)
- Corresponding author
- Reinholdt, Laura G.
- ORCID
- Venue
- Mammalian Genome
- Published
- 2011-09-28
- Volume
- 22
- Issue
- 11-12
- Pages
- 685-691
- ISSN
- 0938-8990 (ISSN-L)
- 1432-1777
- PMC
- PMC3505986
- OpenAlex
- W2030669013
- Cited by
- 186
- References
- 20
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 17 · 2023: 20 · 2022: 13 · 2021: 16 · 2020: 13 · 2019: 12 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 18 · 2014: 12 · 2013: 10 · 2012: 5
- FWCI
- 8.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Mammalian Genome (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- U.S. Public Health Service (CYTO-01)
- National Cancer Institute (#CA34196, P30CA034196)
- National Institute of Dental and Craniofacial Research (DE021034, R15DE021034)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201000006C)
- 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
- Ts65Dn mouse model, Down syndrome, translocation breakpoints, mouse chromosome 16, mouse chromosome 17, gene dosage, synteny, genotyping, paired-end sequencing, de novo assembly
- MeSH terms
- Animals, Base Sequence, Disease Models, Animal, Down Syndrome, Female, Genotype, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Translocation, Genetic, Trisomy, Sequence Alignment, Sequence Analysis, DNA, Gene Dosage, Polymorphism, Single Nucleotide, Mice, High-Throughput Nucleotide Sequencing
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