A transchromosomic rat model with human chromosome 21 shows robust down syndrome features.
Open accessAbstract
Progress in earlier detection and clinical management has increased life expectancy and quality of life in people with Down syndrome (DS). However, no drug has been approved to help individuals with DS live independently and fully. Although rat models could support more robust physiological, behavioral, and toxicology analysis than mouse models during preclinical validation, no DS rat model is available as a result of technical challenges. We developed a transchromosomic rat model of DS, TcHSA21rat, which contains a freely segregating, EGFP-inserted, human chromosome 21 (HSA21) with >93% of its protein-coding genes. RNA-seq of neonatal forebrains demonstrates that TcHSA21rat expresses HSA21 genes and has an imbalance in global gene expression. Using EGFP as a marker for trisomic cells, flow cytometry analyses of peripheral blood cells from 361 adult TcHSA21rat animals show that 81% of animals retain HSA21 in >80% of cells, the criterion for a "Down syndrome karyotype" in people. TcHSA21rat exhibits learning and memory deficits and shows increased anxiety and hyperactivity. TcHSA21rat recapitulates well-characterized DS brain morphology, including smaller brain volume and reduced cerebellar size. In addition, the rat model shows reduced cerebellar foliation, which is not observed in DS mouse models. Moreover, TcHSA21rat exhibits anomalies in craniofacial morphology, heart development, husbandry, and stature. TcHSA21rat is a robust DS animal model that can facilitate DS basic research and provide a unique tool for preclinical validation to accelerate DS drug development.
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TcHSA21rat exhibit learning and memory deficits and other cardinal features of DS such as craniofacial changes and cardiovascular deficits.
“Similar to the MAC21 mouse, TcHSA21rat exhibit learning and memory deficits as well as other cardinal features of DS such as craniofacial changes and cardiovascular deficits.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Kazuki et al., 2022
TcHSA21rat recapitulates the decrease in total brain volume characteristic of DS, and the cerebellum is specifically decreased in size with a simpler foliation pattern.
“Opposed to current mouse models of DS, the TcHSA21rat model recapitulates the decrease in total brain volume that is characteristics in DS. In addition, the cerebellum is specifically decreased in size compared to euploid controls and has a simpler foliation pattern, a feature that is unable to be observed in mouse models.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Kazuki et al., 2022
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Cites
Initial sequencing and comparative analysis of the mouse genome
Mouse Genome Sequencing Consortium (2002) · Nature · doi:10.1038/nature01262 · Cited by 7,187 · see citing works
Extensions of the procrustes method for the optimal superimposition of landmarks
Rohlf, F. J., & Slice, D. (1990) · Systematic Zoology · doi:10.2307/2992207 · Cited by 4,289 · see citing works
Genome sequence of the Brown Norway rat yields insights into mammalian evolution
Gibbs, R. A., Weinstock, G. M., Metzker, M. L., Muzny, D. M., Sodergren, E. J., Scherer, S. E., Scott, G., Steffen, D. L., Worley, K. C., Burch, P. E., et al. (2004) · Nature · doi:10.1038/nature02426 · Cited by 2,147 · see citing works
Estimation of clinical trial success rates and related parameters
Wong, C. H., Siah, K. W., & Lo, A. W. (2019) · Biostatistics · doi:10.1093/biostatistics/kxx069 · Cited by 1,585 · see citing works
Antonarakis, S. E., Skotko, B. G., Rafii, M. S., Strydom, A., Pape, S. E., Bianchi, D. W., Sherman, S. L., & Reeves, R. H. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0143-7 · Cited by 964 · see citing works
Self-citationA mouse model for Down syndrome exhibits learning and behaviour deficits
Reeves, R. H., Irving, N. G., Moran, T. H., Wohn, A., Kitt, C., Sisodia, S. S., Schmidt, C., Bronson, R. T., & Davisson, M. T. (1995) · Nature Genetics · doi:10.1038/ng1095-177 · Cited by 913 · see citing works
Self-citationDown syndrome phenotypes: the consequences of chromosomal imbalance.
Korenberg, J. R., Chen, X. N., Schipper, R. D., Sun, Z., Gonsky, R., Gerwehr, S., Carpenter, N. J., Däumer, C., Dignan, P. S. J., & Distèche, C. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4997 · Cited by 784 · see citing works
Slice, D. E. (2007) · Annual Review of Anthropology · doi:10.1146/annurev.anthro.34.081804.120613 · Cited by 692 · see citing works
Rodent models in neuroscience research: is it a rat race?
Ellenbroek, B., & Youn, J. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.026120 · Cited by 627 · see citing works
Growth and folding of the mammalian cerebral cortex: from molecules to malformations
Sun, T., & Hevner, R. F. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3707 · Cited by 471 · see citing works
Neuroanatomy of Down’s Syndrome: A High-Resolution MRI Study
Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T., & Reiss, A. L. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.10.1659 · Cited by 452 · see citing works
An Aneuploid Mouse Strain Carrying Human Chromosome 21 with down Syndrome Phenotypes.
O'Doherty, A., Ruf, S., Mulligan, C., Hildreth, V., Errington, M. L., Cooke, S., Sesay, A., Modino, S., Vanes, L., Hernandez, D., et al. (2005) · Science · doi:10.1126/science.1114535 · Cited by 434 · see citing works
Moore, T. J., Zhang, H., Anderson, G., & Alexander, G. C. (2018) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2018.3931 · Cited by 356 · see citing works
(1990) · PubMed · Cited by 351 · see citing works
Estimation of the number of people with Down syndrome in the United States
de Graaf, G., Buckley, F., & Skotko, B. G. (2016) · Genetics in Medicine · doi:10.1038/gim.2016.127 · Cited by 338 · see citing works
Domains of genome-wide gene expression dysregulation in Down’s syndrome
Letourneau, A., Santoni, F. A., Bonilla, X., Sailani, M. R., Gonzalez, D., Kind, J., Chevalier, C., Thurman, R., Sandstrom, R. S., Hibaoui, Y., et al. (2014) · Nature · doi:10.1038/nature13200 · Cited by 319 · see citing works
(1993) · PubMed · Cited by 301 · see citing works
Self-citationFerencz, C., Neill, C. A., Boughman, J. A., Rubin, J. D., Brenner, J. I., & Perry, L. W. (1989) · The Journal of Pediatrics · doi:10.1016/s0022-3476(89)80605-5 · Cited by 292 · see citing works
de la Torre, R., de Sola, S., Hernández, G., Farré, M., Pujol, J., Rodríguez, J. C., Espadaler, J. M., Langohr, K., Cuenca‐Royo, A., Príncipe, A., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30034-5 · Cited by 291 · see citing works
Adkins, R. M., Gelke, E. L., Rowe, D. L., & Honeycutt, R. L. (2001) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a003860 · Cited by 283 · see citing works
Species-Specific Transcription in Mice Carrying Human Chromosome 21
Wilson, M. D., Barbosa‐Morais, N. L., Schmidt, D., Conboy, C. B., Vanes, L., Tybulewicz, V. L. J., Fisher, E., Tavaré, S., & Odom, D. T. (2008) · Science · doi:10.1126/science.1160930 · Cited by 280 · see citing works
Discovery and genetic localization of down syndrome cerebellar phenotypes using the Ts65Dn mouse
Baxter, L. L. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.2.195 · Cited by 275 · see citing works
Light/dark Transition Test for Mice
Takao, K., & Miyakawa, T. (2006) · Journal of Visualized Experiments · doi:10.3791/104 · Cited by 268 · see citing works
Functional expression and germline atransmission of a human chromosome fragment in chimaeric mice
Tomizuka, K., Yoshida, H., Uejima, H., Kugoh, H., Sato, K., Ohguma, A., Hayasaka, M., Hanaoka, K., Oshimura, M., & Ishida, I. (1997) · Nature Genetics · doi:10.1038/ng0697-133 · Cited by 267 · see citing works
Self-citationPrenatal Screening for Aneuploidy
Driscoll, D. A., & Gross, S. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmcp0900134 · Cited by 240 · see citing works
A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions
Yu, T., Li, Z., Jia, Z., Clapcote, S. J., Liu, C., Li, S., Asrar, S., Pao, A., Chen, R., Fan, N., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq179 · Cited by 238 · see citing works
Duchon, A., Raveau, M., Chevalier, C., Nalesso, V., Sharp, A. J., & Herault, Y. (2011) · Mammalian Genome · doi:10.1007/s00335-011-9356-0 · Cited by 224 · see citing works
Li, Z., Yu, T., Morishima, M., Pao, A., LaDuca, J., Conroy, J., Nowak, N., Matsui, S.-I., Shiraishi, I., & Yu, Y. E. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm086 · Cited by 218 · see citing works
Use of the light/dark test for anxiety in adult and adolescent male rats
Arrant, A. E., Schramm‐Sapyta, N. L., & Kuhn, C. M. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.05.035 · Cited by 203 · see citing works
Modeling Alzheimer’s disease in transgenic rats
Carmo, S. D., & Cuello, A. C. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-37 · Cited by 203 · see citing works
Tomizuka, K., Shinohara, T., Yoshida, H., Uejima, H., Ohguma, A., Tanaka, S., Sato, K., Oshimura, M., & Ishida, I. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.722 · Cited by 202 · see citing works
Self-citationGenetic dissection of mouse exploratory behaviour
Crusio, W. E. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00280-7 · Cited by 201 · see citing works
Molecular characterization of the translocation breakpoints in the down syndrome mouse model Ts65Dn
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. (2011) · Mammalian Genome · doi:10.1007/s00335-011-9357-z · Cited by 186 · see citing works
Kleschevnikov, A. M., Belichenko, P. V., Faizi, M., Jacobs, L. F., Htun, K. E., Shamloo, M., & Mobley, W. C. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1673-12.2012 · Cited by 174 · see citing works
Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome
Zhu, P., Khatiwada, S., Cui, Y., Reineke, L. C., Dooling, S. W., Kim, J., Li, W., Walter, P., & Costa‐Mattioli, M. (2019) · Science · doi:10.1126/science.aaw5185 · Cited by 169 · see citing works
Mouse models of Down syndrome: gene content and consequences
Gupta, M., Dhanasekaran, A. R., & Gardiner, K. (2016) · Mammalian Genome · doi:10.1007/s00335-016-9661-8 · Cited by 167 · see citing works
Mosaicism for trisomy 21: A review
Papavassiliou, P., Charalsawadi, C., Rafferty, K. A., & Jackson‐Cook, C. K. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36861 · Cited by 166 · see citing works
Braudeau, J., Delatour, B., Duchon, A., Pereira, P. L., Dauphinot, L., de Chaumont, F., Olivo‐Marín, J., Dodd, R. H., Hérault, Y., & Potier, M. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111405366 · Cited by 163 · see citing works
Stores, R., Stores, G., FELLOWS, B. J., & Buckley, S. (1998) · Journal of Intellectual Disability Research · doi:10.1046/j.1365-2788.1998.00123.x · Cited by 162 · see citing works
Global disruption of the cerebellar transcriptome in a Down syndrome mouse model
Saran, N. G. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg217 · Cited by 143 · see citing works
Down Syndrome and Attention-Deficit/Hyperactivity Disorder (ADHD)
Ekstein, S., Glick, B., Weill, M., Kay, B., & Berger, I. (2011) · Journal of Child Neurology · doi:10.1177/0883073811405201 · Cited by 137 · see citing works
Faizi, M., Bader, P. L., Tun, C., Encarnacion, A., Kleschevnikov, A. M., Belichenko, P. V., Saw, N. L., Priestley, M., Tsien, R. W., Mobley, W. C., et al. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.04.011 · Cited by 134 · see citing works
Hedgehog Agonist Therapy Corrects Structural and Cognitive Deficits in a Down Syndrome Mouse Model
Das, I., Park, J. M., Shin, J. H., Jeon, S. K., Lorenzi, H., Linden, D. J., Worley, P. F., & Reeves, R. H. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005983 · Cited by 134 · see citing works
Self-citationOxelgren, U. W., Myrelid, Å., Annerén, G., Ekstam, B., Göransson, C., Holmbom, A., Isaksson, A., Åberg, M., Gustafsson, J., & Fernell, E. (2016) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.13217 · Cited by 130 · 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-citationShinohara, T. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.11.1163 · Cited by 121 · see citing works
Pritchard, M. A., & Kola, I. (1999) · Springer eBooks · doi:10.1007/978-3-7091-6380-1_20 · Cited by 116 · see citing works
Refined human artificial chromosome vectors for gene therapy and animal transgenesis
Kazuki, Y., Hoshiya, H., Takiguchi, M., Abe, S., Iida, Y., Osaki, M., Katoh, M., Hiratsuka, M., Shirayoshi, Y., Hiramatsu, K., et al. (2010) · Gene Therapy · doi:10.1038/gt.2010.147 · Cited by 112 · see citing works
Self-citationHumanising the mouse genome piece by piece
Zhu, F., Nair, R., Fisher, E., & Cunningham, T. J. (2019) · Nature Communications · doi:10.1038/s41467-019-09716-7 · Cited by 110 · see citing works
Accuracy of the clinical diagnosis of Down syndrome.
Devlin, L. K., & Morrison, P. J. (2004) · PubMed · Cited by 99 · see citing works
Euclidean distance matrix analysis: Confidence intervals for form and growth differences
Lele, S. R., & Richtsmeier, J. T. (1995) · American Journal of Physical Anthropology · doi:10.1002/ajpa.1330980107 · Cited by 98 · see citing works
Self-citationGalante, M., Jani, H., Vanes, L., Daniel, H., Fisher, E., Tybulewicz, V. L. J., Bliss, T. V. P., & Morice, É. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp055 · Cited by 89 · see citing works
A COORDINATE‐FREE APPROACH TO THE ANALYSIS OF GROWTH PATTERNS: MODELS AND THEORETICAL CONSIDERATIONS
Richtsmeier, J. T., & Lele, S. R. (1993) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.1993.tb00737.x · Cited by 86 · see citing works
Self-citationEfficient and rapid generation of large genomic variants in rats and mice using CRISMERE
Birling, M., Schaeffer, L., André, P., Lindner, L., Maréchal, D., Ayadi, A., Sorg, T., Pavlovic, G., & Hérault, Y. (2017) · Scientific Reports · doi:10.1038/srep43331 · Cited by 76 · see citing works
Light/dark Transition Test for Mice
Takao, K., & Miyakawa, T. (2006) · Journal of Visualized Experiments · doi:10.3791/104-v · Cited by 76 · see citing works
A Novel and Stable Mouse Artificial Chromosome Vector
Takiguchi, M., Kazuki, Y., Hiramatsu, K., Abe, S., Iida, Y., Takehara, S., Nishida, T., Ohbayashi, T., Wakayama, T., & Oshimura, M. (2012) · ACS Synthetic Biology · doi:10.1021/sb3000723 · Cited by 73 · see citing works
Self-citationUnique Features of the Human Brainstem and Cerebellum
Baizer, J. S. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00202 · Cited by 70 · see citing works
Do, C., Xing, Z., Yu, Y. E., & Tycko, B. (2016) · Epigenomics · doi:10.2217/epi-2016-0138 · Cited by 65 · see citing works
Feyissa, D. D., Aher, Y. D., Engidawork, E., Höger, H., Lübec, G., & Korz, V. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00026 · Cited by 54 · see citing works
Stability of transferred human chromosome fragments in cultured cells and in mice
Shinohara, T., Tomizuka, K., Takehara, S., Yamauchi, K., Katoh, M., Ohguma, A., Ishida, I., & Oshimura, M. (2000) · Chromosome Research · doi:10.1023/a:1026741321193 · Cited by 51 · see citing works
Self-citationAll Creatures Great and Small: New Approaches for Understanding Down Syndrome Genetics
Moyer, A. J., Gardiner, K., & Reeves, R. H. (2021) · Trends in Genetics · doi:10.1016/j.tig.2020.09.017 · Cited by 49 · see citing works
Self-citationHumanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism
Kazuki, Y., Kobayashi, K., Hirabayashi, M., Abe, S., Kajitani, N., Kazuki, K., Takehara, S., Takiguchi, M., Satoh, D., Kuze, J., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808255116 · Cited by 38 · see citing works
Self-citationInoue, J., Mitsuya, K., Maegawa, S., Kugoh, H., Kadota, M., Okamura, D., Shinohara, T., Nishihara, S., Takehara, S., Yamauchi, K., et al. (2001) · Journal of Human Genetics · doi:10.1007/s100380170101 · Cited by 37 · see citing works
Self-citationComparison of modes of ascertainment for mosaic vs complete trisomy 21
Bornstein, E., Lenchner, E., Donnenfeld, A. E., Kapp, S., Keeler, S., & Divon, M. Y. (2009) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2009.01.017 · Cited by 20 · see citing works
Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome
Powell, N. M., Marc Modat, A., Cardoso, M. J., Ma, D., Holmes, H. E., Yu, Y., O’Callaghan, J. M., Cleary, J. O., Sinclair, B., Wiseman, F. K., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162974 · Cited by 19 · see citing works
Ponomartsev, S. V., Sinenko, S. A., Skvortsova, E. V., Liskovykh, M. A., Voropaev, I. N., Savina, M. M., Kuzmin, A. A., Kuzmina, E. Y., Kondrashkina, A. M., Larionov, V., et al. (2020) · Cells · doi:10.3390/cells9040879 · Cited by 19 · see citing works
Zhao, W., Chen, F., Wu, M., Jiang, S., Wu, B., Luo, H., Wen, J., Hu, C., & Yu, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133151 · Cited by 19 · see citing works
Hirabayashi, M., Kato, M., & Hochi, S. (2008) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.57.401 · Cited by 16 · see citing works
Self-citationGao, F., Klinedinst, D. K., Fernandez, F., Cheng, B., Savonenko, A. V., Devenney, B., Li, Y., Wu, D., Pomper, M. G., & Reeves, R. H. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01237-z · Cited by 14 · see citing works
Self-citationAn Invariant Approach to Statistical Analysis of Shapes
Jammalamadaka, S. R. (2002) · Journal of the American Statistical Association · doi:10.1198/016214502760301318 · Cited by 12 · see citing works
Wu, D., Zhang, Y., Cheng, B., Mori, S., Reeves, R. H., & Gao, F. (2021) · Brain Communications · doi:10.1093/braincomms/fcab062 · Cited by 11 · see citing works
Self-citationRat Embryonic Stem Cells: Establishment and Their Use for Transgenesis
Hirabayashi, M., & Hochi, S. (2011) · InTech eBooks · doi:10.5772/14707 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
1 of the 74 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [18]18. [Braudeau, J., Delatour, B., Duchon, A., Pereira, P.L., Dauphinot, L., de Chaumont, F., Olivo-Marin, J.C., Dodd, R.H., He ´rault, Y., and Potier, M.C. (2011). Specific targeting of the GABA-A receptor a 5 subtype by a selective inverse agonist re-](http://refhub.elsevier.com/S0002-9297(21)00470-5/sref18)
- [16]16. [stores cognitive deficits in Down syndrome mice. J. Psychopharmacol. 25 , 1030-1042.](http://refhub.elsevier.com/S0002-9297(21)00470-5/sref18)
- [58]58. [Chapman, R.S., and Hesketh, L.J. (2000). Behavioral phenotype of individuals with Down syndrome. Ment. Retard. Dev. Disabil. Res. Rev. 6 , 84-95.](http://refhub.elsevier.com/S0002-9297(21)00470-5/sref58)
- [69]69. [Ponomartsev, S.V., Sinenko, S.A., Skvortsova, E.V., Liskovykh, M.A., Voropaev, I.N., Savina, M.M., Kuzmin, A.A., Kuzmina, E.Y., Kondrashkina, A.M., Larionov, V., et al. (2020). Human](http://refhub.elsevier.com/S0002-9297(21)00470-5/sref69)
Cited by
Sorted by citations
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
“While there have been dozens of mouse models over the years, the first rat model of DS, TcHSA21rat, was recently created and preliminarily described (Kazuki et al., 2022).”
BackgroundAβ and tau prions feature in the neuropathogenesis of Down syndrome
Condello, C., Maxwell, A. M., Castillo, E., Aoyagi, A., Graff, C., Ingelsson, M., Lannfelt, L., Bird, T. D., Keene, C. D., Seeley, W. W., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2212954119 · Cited by 27 · see citing works
Hashizume, R., Wakita, S., Sawada, H., Takebayashi, S., Kitabatake, Y., Miyagawa, Y., HIROKAWA, Y. S., Imai, H., & Kurahashi, H. (2025) · PNAS Nexus · doi:10.1093/pnasnexus/pgaf022 · Cited by 21 · see citing works
Hypermetabolism in mice carrying a near-complete human chromosome 21
Sarver, D. C., Xu, C., Rodriguez, S., Aja, S. M., Jaffe, A. E., Gao, F., Delannoy, M. R., Periasamy, M., Kazuki, Y., Oshimura, M., et al. (2023) · eLife · doi:10.7554/elife.86023 · Cited by 19 · see citing works
Self-citationWatson, L. A., & Meharena, H. S. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1198129 · Cited by 13 · see citing works
A dynamic in vitro model of Down syndrome neurogenesis with trisomy 21 gene dosage correction
Bansal, P., Banda, E. C., Glatt-Deeley, H. R., Stoddard, C. E., Linsley, J. W., Arora, N., Deleschaux, C., Ahern, D. T., Kondaveeti, Y., Massey, R. E., et al. (2024) · Science Advances · doi:10.1126/sciadv.adj0385 · Cited by 13 · see citing works
Chen, Z., Xu, T., Liu, X., Becker, B., Li, W., Miao, K., Gong, Z., Zhang, R., Huo, Z., Hu, B., et al. (2024) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13649 · Cited by 11 · see citing works
Hawley, L. E., Stringer, M., Deal, A. J., Folz, A., Goodlett, C. R., & Roper, R. J. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106359 · Cited by 10 · see citing works
“TcMAC21 is a new DS mouse model with a near complete human chromosome 21 and DS-like abnormalities (Kazuki et al., 2022).”
BackgroundUltrasonic vocalization phenotypes in the Ts65Dn and Dp(16)1Yey mouse models of Down syndrome
Glass, T. J., Lenell, C., Fisher, E. H., Yang, Q., & Connor, N. P. (2023) · Physiology & Behavior · doi:10.1016/j.physbeh.2023.114323 · Cited by 9 · see citing works
Investigating brain alterations in the Dp1Tyb mouse model of Down syndrome
Navacerrada, M. E. S., Kim, E., Siow, B. M., Ma, D., Gonzalez, L. R., Simmons, C., Hayward, D., Gibbins, D., Singh, N., Strydom, A., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106336 · Cited by 7 · see citing works
Self-citationDeveloping Humanized Animal Models with Transplantable Human iPSC-Derived Cells.
Ma, M., Ge, J.-Y., Nie, Y.-Z., Li, Y.-M., & Zheng, Y.-W. (2024) · Frontiers in Bioscience · doi:10.31083/j.fbl2901034 · Cited by 5 · see citing works
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Cheng, P., Singh, K., Reeves, R. H., & Davoli, T. (2025) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-111723-103557 · Cited by 5 · see citing works
Self-citationRaza, M. A., Folz, A., Victorino, D. B., Xing, Z., Chen, X., Zuo, X., Borden, L. K., Potier, M., Mobley, W. C., Dierssen, M., et al. (2026) · STAR Protocols · doi:10.1016/j.xpro.2026.104717 · Cited by 5 · see citing works
Self-citationMicrocell-mediated chromosome transfer between non-identical human iPSCs
Uno, N., Miyamoto, H., Yamazaki, K., Egawa, M., Kobayashi, H., Kazuki, K., Osaki, M., Suzuki, T., Hamamichi, S., Oshimura, M., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102382 · Cited by 5 · see citing works
Self-citationInfantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations
Stafstrom, C. E., & Shao, L. (2024) · Children · doi:10.3390/children11121513 · Cited by 5 · see citing works
Hiramuki, Y., Abe, S., Uno, N., Kazuki, K., Takata, S., Miyamoto, H., Takayama, H., Morimoto, K., Takehara, S., Osaki, M., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-31481-3 · Cited by 5 · see citing works
Self-citationLlambrich, S., Tielemans, B., Saliën, E., Atzori, M., Wouters, K., Bulck, V. V., Platt, M., Vanherp, L., Fernandez, N. G., de la Fuente, L. G., et al. (2024) · eLife · doi:10.7554/elife.89763.3 · Cited by 5 · see citing works
Zeng, P., Ge, X., & Li, Z. (2023) · Plants · doi:10.3390/plants12102029 · Cited by 5 · see citing works
Advances in keratoconus animal models: From genetics to biomechanics
Zou, Z., Li, S., & Zhang, H. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110330 · Cited by 4 · see citing works
Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome
Szabó, C. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00584 · Cited by 4 · see citing works
A new Down syndrome rat model races forward
Roper, R. J., & Goodlett, C. R. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.05.001 · Cited by 3 · see citing works
Ganguly, B. B., & Kadam, N. N. (2024) · Gene Reports · doi:10.1016/j.genrep.2024.102106 · Cited by 3 · see citing works
Singh, N., Reeves, R. H., & Richtsmeier, J. T. (2025) · Journal of Anatomy · doi:10.1111/joa.70066 · Cited by 1 · see citing works
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Wakayama, S., Araki, R., Sunayama, M., Yamagata, K., Tokoro, M., Nagamatsu, G., Abe, M., & Wakayama, T. (2026) · Scientific Reports · doi:10.1038/s41598-026-55500-1 · Cited by 1 · see citing works
Llambrich, S., Tielemans, B., Saliën, E., Atzori, M., Wouters, K., Bulck, V. V., Platt, M., Vanherp, L., Fernandez, N. G., de la Fuente, L. G., et al. (2023) · eLife · doi:10.1101/2023.07.31.551282 · Cited by 6 · see citing works
Satofuka, H., Abe, S., Moriwaki, T., Okada, A., Kazuki, K., Hamamichi, S., Hiratsuka, M., Hirabayashi, M., Nakamura, K., Sakuma, T., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.26.609625 · Cited by 1 · see citing works
Self-citationInvestigating Brain Alterations in the Dp1Tyb Mouse Model of Down SyndromePreprint
Navacerrada, M. E. S., Kim, E., Siow, B. M., Ma, D., Gonzalez, L. R., Simmons, C., Hayward, D., Gibbins, D., Singh, N., Strydom, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.26.550698
Self-citationDevelopment of Cortical Neuron Heterogeneity and Impact of Neurodevelopmental Disorders
Li, Z., Tylerand, W. A., & Haydar, T. F. (2023) · doi:10.1002/9781119860914.ch12
Llambrich, S., Tielemans, B., Saliën, E., Atzori, M., Wouters, K., Bulck, V. V., Platt, M., Vanherp, L., Fernandez, N. G., de la Fuente, L. G., et al. (2023) · eLife · doi:10.7554/elife.89763.1
Llambrich, S., Tielemans, B., Saliën, E., Atzori, M., Wouters, K., Bulck, V. V., Platt, M., Vanherp, L., Fernandez, N. G., de la Fuente, L. G., et al. (2024) · eLife · doi:10.7554/elife.89763.2
Suman, L., Sharif, M., Murthy, P. S., Seenappa, C., & Hamsa, K. R. (2024) · International Journal of Agriculture Extension and Social Development · doi:10.33545/26180723.2024.v7.i5f.649
Recent Progress in Basic Research on Cardiovascular Diseases Associated with Down Syndrome
Ishida, H. (2023) · Japanese Society of Pediatric Cardiology and Cardiac Surgery · doi:10.9794/jspccs.39.200
Humanized Rodent Models of Down Syndrome
Reeves, R. H. (2025) · Springer eBooks · doi:10.1007/978-3-031-78611-2_3
Self-citationBartesaghi, R., Chen, X., Johnstone, A. D., Das, U., & Mobley, W. C. (2025) · Springer eBooks · doi:10.1007/978-3-031-89307-0_19
Associations Among miR-33, APOE ε4, and Metabolic Markers in Down Syndrome YouthPreprint
Ocampo, K. E., Espinoza, W. G., Acosta, T. S., Villalobos, S. A., Ontiveros, S. A. B., López, R. Z., Villarreal, M. P., Calderón-Zamora, L., Guadrón‐Llanos, A. M., Rojo, C. A., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-8845542/v1
Craniofacial analysis of Down syndrome rodent models
Saavedra, J. T. A. (2024) · doi:10.70675/064b45abz323ez478ez93ddz8ce0747170c2
Humanized Animal Models in Biological Research
Nurboo, S., Yadav, S., Ranwa, S., & Nazir, A. (2026) · Springer eBooks · doi:10.1007/978-981-92-0038-2_7
Domenico, F. D., Marzia Perluigi, A., Tramutola, A., Bacalini, M. G., Victorino, D. B., Barroeta, I., Bartesaghi, R., Carfì, A., Carmona‐Iragui, M., Cohen, A. D., et al. (2026) · NeuroMolecular Medicine · doi:10.1007/s12017-026-08921-0
Self-citationTransforming Life Science Through Chromosome‐Level Genome Assemblies
Kon, T., Kataoka, K., Luo, Y., Wibisana, J. N., Toga, K., Uno, N., Monden, Y., & Hamada, M. (2026) · Genes to Cells · doi:10.1111/gtc.70145
Plećaš, A., Gough, G., Kunštek, S., Babić, M., Murray, A., Nižetić, D., & Alić, I. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1963992
- Authors
- Kazuki, Y., Gao, F. J., Yamakawa, M., Hirabayashi, M., Kazuki, K., Kajitani, N., Miyagawa-Tomita, S., Abe, S., Sanbo, M., Hara, H., Kuniishi, H., Ichisaka, S., Hata, Y., Koshima, M., Takayama, H., Takehara, S., Nakayama, Y., Hiratsuka, M., Iida, Y., Matsukura, S., Noda, N., Li, Y., Moyer, A. J., Cheng, B., Singh, N., Richtsmeier, J. T., Oshimura, M., & Reeves, R. H.
- Affiliations
- Chromosome Engineering Research Center (JP)
- Johns Hopkins University (US)
- National Institute for Physiological Sciences (JP)
- Trans Chromosomics, Inc. (Japan) (JP)
- Tottori University (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- California State University, Sacramento (US)
- Pennsylvania State University (US)
- Corresponding author
- Kazuki, Yasuhiro
- Reeves, Roger H.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 109
- Issue
- 2
- Pages
- 328-344
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC8874226
- OpenAlex
- W4206983653
- Cited by
- 41
- References
- 74
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 11 · 2023: 13 · 2022: 3
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Mitsubishi Foundation (R01HD038384, R21HD098540)
- Core Research for Evolutional Science and Technology (JPMJCR18S4)
- National Institutes of Health (R21HD098540, R01HD038384)
- Japan Science and Technology Agency
- National Institute for Physiological Sciences (17-252)
- National Institute of Advanced Industrial Science and Technology
- Tottori University
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Down syndrome, chromosome 21, trisomy, rat model, cerebellar foliation, learning and memory impairment, anxiety, hyperactivity, brain structure, craniofacial anomalies, heart development, gene expression imbalance, preclinical drug development
- MeSH terms
- Animals, Anxiety, Cerebellum, Chromosomes, Human, Pair 21, Disease Models, Animal, Down Syndrome, Female, Humans, Hyperkinesis, Learning, Male, Organ Size, Posture, Mutagenesis, Insertional, Prosencephalon, Genes, Reporter, Founder Effect, Green Fluorescent Proteins, Rats, Rats, Transgenic, Karyotype
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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