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Cited by 224Down syndrome and intellectual disability researchGenomic variations and chromosomal abnormalitiesGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling down syndrome

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Duchon, Arnaud, Raveau, Matthieu, Chevalier, Claire, Nalesso, Valérie, Sharp, Andrew J., Herault, Yann·2011·Mammalian Genome
DOI 10.1007/s00335-011-9356-0PMC PMC3224224
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Abstract

Down syndrome (DS) is the most frequent genetic disorder leading to intellectual disabilities and is caused by three copies of human chromosome 21. Mouse models are widely used to better understand the physiopathology in DS or to test new therapeutic approaches. The older and the most widely used mouse models are the trisomic Ts65Dn and the Ts1Cje mice. They display deficits similar to those observed in DS people, such as those in behavior and cognition or in neuronal abnormalities. The Ts65Dn model is currently used for further therapeutic assessment of candidate drugs. In both models, the trisomy was induced by reciprocal chromosomal translocations that were not further characterized. Using a comparative genomic approach, we have been able to locate precisely the translocation breakpoint in these two models and we took advantage of this finding to derive a new and more efficient Ts65Dn genotyping strategy. Furthermore, we found that the translocations introduce additional aneuploidy in both models, with a monosomy of seven genes in the most telomeric part of mouse chromosome 12 in the Ts1Cje and a trisomy of 60 centromeric genes on mouse chromosome 17 in the Ts65Dn. Finally, we report here the overexpression of the newly found aneuploid genes in the Ts65Dn heart and we discuss their potential impact on the validity of the DS model.

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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 Duchon et al., 2011

    The Discussion identifies an extra trisomic segment of mouse chromosome 17 in Ts65Dn containing 60 annotated genes nonhomologous to Hsa21, supporting the stated limitation. The Results use 35 for genes from that interval found on the Affymetrix array, not for the total number of protein-coding genes; our copy therefore does not establish the claimed count. (LLM, conf=0.88)

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  • Like the majority of individuals with Down syndrome, Ts65Dn has an extra freely segregating marker chromosome that carries ∼119 genes triplicated from MMU16.

    “Therefore, like the majority of individuals with DS, Ts65Dn has an extra freely segregating marker chromosome that carries ∼119 genes triplicated from MMU16 (Duchon et al., 2011).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Duchon et al., 2011

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Research works printed but not linked: 51

  1. Adayev T Chen-Hwang MC Murakami N Wang R Hwang YW MNB/DYRK1A phosphorylation regulates the interactions of synaptojanin 1 with endocytic accessory proteins Biochem Biophys Res Commun 2006 351 1060 1065 10.1016/j.bbrc.2006.10.169 17097615 PMC1750923 · DOI
  2. Belichenko PV Masliah E Kleschevnikov AM Villar AJ Epstein CJ Salehi A Mobley WC Synaptic structural abnormalities in the Ts65Dn mouse model of Down syndrome J Comp Neurol 2004 480 281 298 10.1002/cne.20337 15515178 · DOI · Paper page
  3. Belichenko PV Kleschevnikov AM Masliah E Wu CB Takimoto-Kimura R Salehi A Mobley WC Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of Down syndrome J Comp Neurol 2009 512 453 466 10.1002/cne.21895 19034952 PMC8480942 · DOI · Paper page
  4. Braudeau J Delatour B Duchon A Lopes-Pereira P Dauphinot L de Chaumont F Olivo-Marin JC Dodd RH Herault Y Potier MC Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice J Psychopharmacol 2011 25 1030 1042 10.1177/0269881111405366 21693554 PMC3160204 · DOI
  5. Brault V Pereira P Duchon A Hérault Y Modeling chromosomes in mouse to explore the function of genes, genomic disorders, and chromosomal organization PLoS Genet 2006 2 e86 10.1371/journal.pgen.0020086 16839184 PMC1500809 · DOI
  6. Brault V, Besson V, Magnol L, Duchon A, Hérault Y (2007) Cre/loxP-mediated chromosome engineering of the mouse genome. Handb Exp Pharmacol (178):29–48 17203650
  7. Contestabile A Benfenati F Gasparini L Communication breaks-Down: from neurodevelopment defects to cognitive disabilities in Down syndrome Prog Neurobiol 2010 91 1 22 10.1016/j.pneurobio.2010.01.003 20097253 · DOI · Paper page
  8. Costa ACS Scott-McKean JJ Stasko MR Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test Neuropsychopharmacology 2008 33 1624 1632 10.1038/sj.npp.1301535 17700645 · DOI
  9. Davisson MT Schmidt C Akeson EC Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome Prog Clin Biol Res 1990 360 263 280 2147289
  10. Davisson MT Schmidt C Reeves RH Irving NG Akeson EC Harris BS Bronson RT Segmental trisomy as a mouse model for Down syndrome Prog Clin Biol Res 1993 384 117 133 8115398
  11. Dierssen M Herault Y Estivill X Aneuploidy: from a physiological mechanism of variance to Down syndrome Physiol Rev 2009 89 887 920 10.1152/physrev.00032.2007 19584316 · DOI
  12. Duchon A Besson V Pereira PL Magnol L Hérault Y Inducing segmental aneuploid mosaicism in the mouse through targeted asymmetric sister chromatid event of recombination Genetics 2008 180 51 59 10.1534/genetics.108.092312 18757940 PMC2535701 · DOI
  13. Duchon A Pothion S Brault V Sharp AJ Tybulewicz VLJ Fisher EMC Herault Y The telomeric part of the human chromosome 21 from Cstb to Prmt2 is not necessary for the locomotor and short-term memory deficits observed in the Tc1 mouse model of Down syndrome Behav Brain Res 2011 217 271 281 10.1016/j.bbr.2010.10.023 21047530 PMC3590452 · DOI
  14. Fernandez F Morishita W Zuniga E Nguyen J Blank M Malenka RC Garner CC Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome Nat Neurosci 2007 10 411 413 17322876
  15. Goto K Kurashima R Gokan H Inoue N Ito I Watanabe S Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in IV mice PLoS One 2010 5 11 e15468 10.1371/journal.pone.0015468 21103351 PMC2984506 · DOI
  16. Hill CA Sussan TE Reeves RH Richtsmeier JT Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic “Down syndrome” mice Am J Med Genet A 2009 149A 2158 2165 10.1002/ajmg.a.33012 19764029 PMC2903219 · DOI
  17. Hoelter SM Dalke C Kallnik M Becker L Horsch M Schrewe A Favor J Klopstock T Beckers J Ivandic B Gailus-Durner V Fuchs H de Angelis MH Graw J Wurst W “Sighted C3H” mice: a tool for analysing the influence of vision on mouse behaviour? Front Biosci 2008 13 5810 5823 10.2741/3118 18508624 · DOI
  18. Huang da W Sherman BT Lempicki RA Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists Nucleic Acids Res 2009 37 1 13 10.1093/nar/gkn923 19033363 PMC2615629 · DOI · Paper page
  19. Huang da W Sherman BT Lempicki RA Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources Nat Protoc 2009 4 44 57 10.1038/nprot.2008.211 19131956 · DOI · Paper page
  20. Huang TT Yasunami M Carlson EJ Gillespie AM Reaume AG Hoffman EK Chan PH Scott RW Epstein CJ Superoxide-mediated cytotoxicity in superoxide dismutase-deficient fetal fibroblasts Arch Biochem Biophys 1997 344 424 432 10.1006/abbi.1997.0237 9264557 · DOI
  21. Hussain NK Jenna S Glogauer M Quinn CC Wasiak S Guipponi M Antonarakis SE Kay BK Stossel TP Lamarche-Vane N McPherson PS Endocytic protein intersectin-I regulates actin assembly via Cdc42 and N-WASP Nat Cell Biol 2001 3 927 932 10.1038/ncb1001-927 11584276 · DOI
  22. Irizarry RA Hobbs B Collin F Beazer-Barclay YD Antonellis KJ Scherf U Speed TP Exploration, normalization, and summaries of high density oligonucleotide array probe level data Biostatistics 2003 4 249 264 10.1093/biostatistics/4.2.249 12925520 · DOI · Paper page
  23. Kleschevnikov AM Belichenko PV Villar AJ Epstein CJ Malenka RC Mobley WC Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome J Neurosci 2004 24 8153 8160 10.1523/JNEUROSCI.1766-04.2004 15371516 PMC6729789 · DOI · Paper page
  24. Laffaire J Rivals I Dauphinot L Pasteau F Wehrle R Larrat B Vitalis T Moldrich RX Rossier J Sinkus R Herault Y Dusart I Potier MC Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development BMC Genomics 2009 10 15 10.1186/1471-2164-10-138 19331679 PMC2678156 · DOI
  25. Lee SY Wenk MR Kim Y Naim AC De Camilli P Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses Proc Natl Acad Sci USA 2004 101 546 551 10.1073/pnas.0307813100 14704270 PMC327184 · DOI
  26. Li Z Yu T Morishima M Pao A LaDuca J Conroy J Nowak N Matsui S-I Shiraishi I Yu YE Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities Hum Mol Genet 2007 16 1359 1366 10.1093/hmg/ddm086 17412756 · DOI · Paper page
  27. Liu DP, Schmidt C, Billings T, Davisson MT (2003) Quantitative PCR genotyping assay for the Ts65Dn mouse model of Down syndrome. Biotechniques 35:1170–1174, 1176 14682051
  28. Lorenzi H Duvall N Cherry SM Reeves RH Roper RJ PCR prescreen for genotyping the Ts65Dn mouse model of Down syndrome Biotechniques 2010 48 35 37 10.2144/000113342 20095097 PMC2955870 · DOI
  29. Mobley AK Tchaicha JH Shin J Hossain MG McCarty JH Beta 8 integrin regulates neurogenesis and neurovascular homeostasis in the adult brain J Cell Sci 2009 122 1842 1851 10.1242/jcs.043257 19461074 PMC2694619 · DOI
  30. Moldrich RX Dauphinot L Laffaire J Rossier J Potier MC Down syndrome gene dosage imbalance on cerebellum development Prog Neurobiol 2007 82 87 94 10.1016/j.pneurobio.2007.02.006 17408845 · DOI
  31. Moran TH Capone GT Knipp S Davisson MT Reeves RH Gearhart JD The effects of piracetam on cognitive performance in a mouse model of Down’s syndrome Physiol Behav 2002 77 403 409 10.1016/S0031-9384(02)00873-9 12419416 · DOI
  32. Nemoto Y Wenk MR Watanabe M Daniell L Murakami T Ringstad N Yamada H Takei K De Camilli P Identification and characterization of a synaptojanin 2 splice isoform predominantly expressed in nerve terminals J Biol Chem 2001 276 41133 41142 10.1074/jbc.M106404200 11498538 · DOI
  33. O’Doherty A Ruf S Mulligan C Hildreth V Errington ML Cooke S Sesay A Modino S Vanes L Hernandez D Linehan JM Sharpe PT Brandner S Bliss TVP Henderson DJ Nizetic D Tybulewicz VLJ Fisher EMC An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes Science 2005 309 2033 2037 10.1126/science.1114535 16179473 PMC1378183 · DOI · Paper page
  34. Olson LE Richtsmeier JT Leszl J Reeves RH A chromosome 21 critical region does not cause specific Down syndrome phenotypes Science 2004 306 687 690 10.1126/science.1098992 15499018 PMC4019810 · DOI
  35. Pereira PL Magnol L Sahún I Brault V Duchon A Prandini P Gruart A Bizot JC Chadefaux-Vekemans B Deutsch S Trovero F Delgado-García JM Antonarakis SE Dierssen M Herault Y A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome Hum Mol Genet 2009 18 4756 4769 10.1093/hmg/ddp438 19783846 PMC2778371 · DOI
  36. Popov VI Kleschevnikov AM Klimenko OA Stewart MG Belichenko PV Three-dimensional synaptic ultrastructure in the dentate gyrus and hippocampal area CA3 in the Ts65Dn mouse model of Down syndrome J Comp Neurol 2011 519 1338 1354 10.1002/cne.22573 21452200 · DOI
  37. Pruitt KD Tatusova T Maglott DR NCBI reference sequence project: update and current status Nucleic Acids Res 2003 31 34 37 10.1093/nar/gkg111 12519942 PMC165558 · DOI
  38. Ramos B Gaudilliere B Bonni A Gill G Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation Proc Natl Acad Sci USA 2007 104 9882 9887 10.1073/pnas.0701946104 17535924 PMC1887555 · DOI
  39. Reeves RH Irving NG Moran TH Wohn A Kitt C Sisodia SS Schmidt C Bronson RT Davisson MT A mouse model for Down syndrome exhibits learning and behaviour deficits Nat Genet 1995 11 177 184 10.1038/ng1095-177 7550346 · DOI · Paper page
  40. Roper RJ Baxter LL Saran NG Klinedinst DK Beachy PA Reeves RH Defective cerebellar response to mitogenic Hedgehog signaling in Down [corrected] syndrome mice Proc Natl Acad Sci USA 2006 103 1452 1456 10.1073/pnas.0510750103 16432181 PMC1360600 · DOI
  41. Rothermel BA Vega RB Williams RS The role of modulatory calcineurin-interacting proteins in calcineurin signaling Trends Cardiovasc Med 2003 13 15 21 10.1016/S1050-1738(02)00188-3 12554096 · DOI
  42. Rueda N Florez J Martinez-Cue C Chronic pentylenetetrazole but not donepezil treatment rescues spatial cognition in Ts65Dn mice, a model for Down syndrome Neurosci Lett 2008 433 22 27 10.1016/j.neulet.2007.12.039 18226451 · DOI
  43. Salehi A, Faizi M, Colas D, Valletta J, Laguna J, Takimoto-Kimura R, Kleschevnikov A, Wagner SL, Aisen P, Shamloo M, Mobley WC (2009) Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome. Sci Transl Med 1:7ra17 20368182
  44. Supp DM Witte DP Potter SS Brueckner M Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice Nature 1997 389 963 966 10.1038/40140 9353118 PMC1800588 · DOI
  45. Terawaki S Kitano K Mori T Zhai Y Higuchi Y Itoh N Watanabe T Kaibuchi K Hakoshima T The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module EMBO J 2010 29 236 250 10.1038/emboj.2009.323 19893486 PMC2775898 · DOI
  46. Villar AJ Belichenko PV Gillespie AM Kozy HM Mobley WC Epstein CJ Identification and characterization of a new Down syndrome model, Ts Rb(12.17(16)) 2Cje, resulting from a spontaneous Robertsonian fusion between T(17(16))65Dn and mouse Chromosome 12 Mamm Genome 2005 16 79 90 10.1007/s00335-004-2428-7 15859352 · DOI
  47. Voronov SV Frere SG Giovedi S Pollina EA Borel C Zhang H Schmidt C Akeson EC Wenk MR Cimasoni L Arancio O Davisson MT Antonarakis SE Gardiner K De Camilli P Di Paolo G Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down’s syndrome Proc Natl Acad Sci USA 2008 105 9415 9420 10.1073/pnas.0803756105 18591654 PMC2453748 · DOI · Paper page
  48. Yu T Li Z Jia Z Clapcote SJ Liu C Li S Asrar S Pao A Chen R Fan N Carattini-Rivera S Bechard AR Spring S Henkelman RM Stoica G Matsui S-I Nowak NJ Roder JC Chen C Bradley A Yu YE A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions Hum Mol Genet 2010 19 2780 2791 10.1093/hmg/ddq179 20442137 PMC2893810 · DOI
  49. Yu T Liu CH Belichenko P Clapcote SJ Li SM Pao AN Kleschevnikov A Bechard AR Asrar S Chen RQ Fan N Zhou ZY Jia ZP Chen C Roder JC Liu B Baldini A Mobley WC Yu YE Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice Brain Res 2010 1366 162 171 10.1016/j.brainres.2010.09.107 20932954 PMC3027718 · DOI · Paper page
  50. Zembrzycki A Griesel G Stoykova A Mansouri A Genetic interplay between the transcription factors Sp8 and Emx2 in the patterning of the forebrain Neural Dev 2007 2 8 10.1186/1749-8104-2-8 17470284 PMC1868949 · DOI
  51. Zhou X Qyang Y Kelsoe JR Masliah E Geyer MA Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant mice Genes Brain Behav 2007 6 269 276 10.1111/j.1601-183X.2006.00256.x 16899055 · DOI

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Authors
Duchon, A., Raveau, M., Chevalier, C., Nalesso, V., Sharp, A. J., & Herault, Y.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Icahn School of Medicine at Mount Sinai (US)
ORCID
Venue
Mammalian Genome
Publisher
Springer Science and Business Media LLC
Published
2011-09-28
Volume
22
Issue
11-12
Pages
674-684
ISSN
  • 0938-8990 (ISSN-L)
  • 1432-1777
DOI
10.1007/s00335-011-9356-0
PMC
PMC3224224
OpenAlex
W1987510426
Cited by
224
References
3
Citations by year
2026: 14 · 2025: 17 · 2024: 17 · 2023: 20 · 2022: 18 · 2021: 21 · 2020: 15 · 2019: 21 · 2018: 13 · 2017: 12 · 2016: 12 · 2015: 14 · 2014: 12 · 2013: 10 · 2012: 7
FWCI
9.12
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Mammalian Genome (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc)
Funders
  • European Commission (037627, LSHG-CT-2006-037627)
  • Institut National de la Santé et de la Recherche Médicale
  • Université de Strasbourg
  • Centre National de la Recherche Scientifique
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
Down syndrome, Ts65Dn mouse model, translocation breakpoints, aneuploidy, genotyping strategies, comparative genomics
MeSH terms
Animals, Cell Line, Disease Models, Animal, Down Syndrome, Genotype, Mice, Inbred BALB C, Mutation, Myocardium, Translocation, Genetic, Trisomy, Oligonucleotide Array Sequence Analysis, Gene Duplication, Mice, DNA Breaks, Comparative Genomic Hybridization

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