A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21.
Open accessAbstract
Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we “clone” the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc(HSA21q;MAC)1Yakaz (“TcMAC21”). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In MAC21, the cerebellum is decreased in volume at 4-5 months, there is no change in hippocampal volume, and total brain volume is significantly larger in trisomic mice.
“Similar to human and Ts65Dn data, in MAC21 the cerebellum is decreased in volume compared to euploid at 4–5 months of age. However, there is no change in hippocampal volume and total brain volume is significantly larger in the trisomic mice.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Kazuki et al., 2020
The Results section (brain morphometric phenotypes; page unavailable) reports that ~4.5-month-old TcMAC21 mice had significantly larger total brain volume and a significantly smaller cerebellar percentage of brain volume than euploid mice. The Figure 4 caption says hippocampal percentage was analyzed, but the passages in our copy do not state that hippocampal volume was unchanged. The reported cerebellar decrease is relative to total brain volume, not an explicitly reported decrease in absolute volume. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMAC21 appears to have an increase in brain volume, the opposite of what is observed in humans.
“MAC21, though not well characterized, appears to have an increase in brain volume, the opposite of what is observed in humans.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Kazuki et al., 2020
The Results section (‘TcMAC21 mice have abnormalities in heart, brain and skull’; page unavailable) reports slightly larger total brain volume in young adult TcMAC21 mice than in euploid controls. It mentions cerebellar hypoplasia in people with Down syndrome, but does not establish the claimed opposite pattern for total brain volume in humans. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMAC21 show learning and memory deficits.
“In addition to modeling the genetics of DS, they also show some of the same behavioral deficits in learning and memory.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Kazuki et al., 2020
MAC21 recapitulates some phenotypes described in individuals with DS.
“The transchromosomic mouse model, MAC21, has undergone preliminary characterization and recapitulates some of the phenotypes described in individuals with DS (Kazuki et al., 2020).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Kazuki et al., 2020
MAC21 recapitulate non-neuronal phenotypes such as skeletal changes and cardiovascular abnormalities.
“Like Dp1Tyb/Dp(16)1Yey, they appear to recapitulate some of the non-neuronal phenotypes associated with DS such as skeletal changes and cardiovascular abnormalities.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Kazuki et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
ISCN 1995 An international system for human cytogenetic nomenclature
Mitelman, F. (1995) · Cited by 1,930 · see citing works
The DNA sequence of human chromosome 21
Hattori, M., Fujiyama, A., Taylor, T. D., Watanabe, H., Yada, T., Park, H.-S., Toyoda, A., Ishii, K., Totoki, Y., Choi, D., et al. (2000) · Nature · doi:10.1038/35012518 · Cited by 1,475 · 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
Kleschevnikov, A. M., Belichenko, P. V., Villar, A. J., Epstein, C. J., Malenka, R. C., & Mobley, W. C. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1766-04.2004 · Cited by 459 · 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
Molecular mapping of alzheimer‐type dementia in Down's syndrome
Prasher, V. P., Farrer, M. J., Kessling, A. M., Fisher, E. M. C., West, R. J., Barber, P. C., & Butler, A. C. (1998) · Annals of Neurology · doi:10.1002/ana.410430316 · Cited by 414 · see citing works
Sleegers, K., Brouwers, N., Gijselinck, I., Theuns, J., Goossens, D., Wauters, J., Del‐Favero, J., Cruts, M., van Duijn, C. M., & Broeckhoven, C. V. (2006) · Brain · doi:10.1093/brain/awl203 · Cited by 406 · see citing works
(1990) · PubMed · Cited by 351 · see citing works
The Consequences of Chromosome Imbalance
Epstein, C. J. (1986) · Cambridge University Press eBooks · doi:10.1017/cbo9780511529702 · Cited by 309 · see citing works
Hippocampal cytotoxic lesion effects on species-typical behaviours in mice
Deacon, R. M. J., Croucher, A. P., & Rawlins, J. N. P. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00401-6 · Cited by 307 · see citing works
(1993) · PubMed · Cited by 301 · see citing works
Self-citationDiscovery 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
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-citationParallels of craniofacial maldevelopment in down syndrome and Ts65Dn mice
Richtsmeier, J. T., Baxter, L. L., & Reeves, R. H. (2000) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(200002)217:2 · Cited by 255 · 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
Understanding the Basis for Down Syndrome Phenotypes
Roper, R. J., & Reeves, R. H. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020050 · Cited by 233 · see citing works
Self-citationDeLorey, T. M., Sahbaie, P., Hashemi, E., Homanics, G. E., & Clark, J. D. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.09.009 · Cited by 224 · 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
Altered long-term potentiation in the young and old Ts65Dn mouse, a model for down syndrome
Siarey, R. J., Stoll, J., Rapoport, S. I., & Galdzicki, Z. (1997) · Neuropharmacology · doi:10.1016/s0028-3908(97)00157-3 · Cited by 222 · see citing works
Gardiner, K., Fortna, A., Bechtel, L. J., & Davisson, M. T. (2003) · Gene · doi:10.1016/s0378-1119(03)00769-8 · Cited by 203 · 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
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
Olson, L. E., Roper, R. J., Baxter, L. L., Carlson, E. J., Epstein, C. J., & Reeves, R. H. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20079 · Cited by 165 · see citing works
Self-citationBraudeau, 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
Restoration of Norepinephrine-Modulated Contextual Memory in a Mouse Model of Down Syndrome
Salehi, A., Faizi, M., Colas, D., Valletta, J. S., Laguna, J., Takimoto‐Kimura, R., Kleschevnikov, A. M., Wagner, S. L., Aisen, P. S. S., Shamloo, M., et al. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000258 · Cited by 159 · see citing works
Cerebellar Volume in Adults With Down Syndrome
Aylward, E., Habbak, R., Warren, A. C., Pulsifer, M. B., Barta, P. E., Jerram, M. W., & Pearlson, G. D. (1997) · Archives of Neurology · doi:10.1001/archneur.1997.00550140077016 · Cited by 147 · 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
Shinohara, T. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.11.1163 · Cited by 121 · see citing works
Genomic Instability Within Centromeres of Interspecific Marsupial Hybrids
Metcalfe, C. J., Bulazel, K. V., Ferreri, G. C., Schroeder-Reiter, E., Wanner, G., Rens, W., Obergfell, C. J., Eldridge, M. D. B., & O'Neill, R. J. W. (2007) · Genetics · doi:10.1534/genetics.107.082313 · 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-citationHoshiya, H., Kazuki, Y., Abe, S., Takiguchi, M., Kajitani, N., Watanabe, Y., Yoshino, T., Shirayoshi, Y., Higaki, K., Messina, G., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.253 · Cited by 109 · see citing works
Self-citationAneuploidy Causes Non-genetic Individuality
Beach, R. R., Ricci-Tam, C., Brennan, C. M., Moomau, C. A., Hsu, P.-H., Hua, B., Silberman, R. E., Springer, M., & Amon, A. (2017) · Cell · doi:10.1016/j.cell.2017.03.021 · Cited by 109 · see citing works
Ishihara, K., Amano, K., Takaki, E., Shimohata, A., Sago, H., Epstein, C. J., & Yamakawa, K. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp176 · Cited by 106 · see citing works
Lana‐Elola, E., Watson-Scales, S., Slender, A., Gibbins, D., Martineau, A., Douglas, C., Mohun, T. J., Fisher, E., & Tybulewicz, V. L. J. (2016) · eLife · doi:10.7554/elife.11614 · Cited by 105 · see citing works
Gribble, S. M., Wiseman, F. K., Clayton, S., Prigmore, E., Langley, E., Yang, F., Maguire, S., Fu, B., Rajan, D., Sheppard, O., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060482 · Cited by 102 · see citing works
Gallagher, J. J., Minogue, A. M., & Lynch, M. A. (2012) · Neurodegenerative Diseases · doi:10.1159/000337458 · Cited by 99 · see citing works
Zhang, J., Peng, Q., Li, Q., Jahanshad, N., Hou, Z., Jiang, M., Masuda, N., Langbehn, D. R., Miller, M. I., Mori, S., et al. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.10.027 · Cited by 94 · see citing works
An improved method for preparing G-banded chromosomes from mouse peripheral blood
Davisson, M. T., & Akeson, E. C. (2008) · Cytogenetics and Cell Genetics · doi:10.1159/000132432 · Cited by 75 · see citing works
International standing committee on human cytogenetic nomenclature
Mitelman, F. (1996) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(96)90076-x · Cited by 73 · 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-citationLi, H., Cherry, S. M., Klinedinst, D. K., DeLeon, V. B., Redig, J. K., Reshey, B., Chin, M. T., Sherman, S. L., Maslen, C. L., & Reeves, R. H. (2012) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.111.960872 · Cited by 71 · see citing works
Self-citationSize and shape analysis of landmark data
Dryden, I. L., & Mardia, K. V. (1992) · Biometrika · doi:10.1093/biomet/79.1.57 · Cited by 70 · see citing works
Body Composition and BMI Growth Charts in Children With Down Syndrome
Hatch-Stein, J. A., Zemel, B. S., Prasad, D., Kalkwarf, H. J., Pipan, M. E., Magge, S. N., & Kelly, A. T. (2016) · PEDIATRICS · doi:10.1542/peds.2016-0541 · Cited by 61 · see citing works
Survival of children with mosaic Down syndrome
Shin, M., Siffel, C., & Correa, A. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33295 · Cited by 60 · see citing works
Down's syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse
Dunlevy, L. P. E., Bennett, M. W., Slender, A., Lana‐Elola, E., Tybulewicz, V. L. J., Fisher, E., & Mohun, T. J. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq193 · Cited by 57 · see citing works
Chromosomal radiosensitivity in Down's syndrome.
Ms, S., & Tonomura, A. (1969) · PubMed · Cited by 57 · see citing works
Birger, Y., Goldberg, L., Chlon, T. M., Goldenson, B., Muler, I., Schiby, G., Jacob–Hirsch, J., Rechavi, G., Crispino, J. D., & Izraeli, S. (2013) · Blood · doi:10.1182/blood-2012-10-460998 · Cited by 56 · see citing works
Kolb, B. E., & Whishaw, I. Q. (1985) · Behavioral Neuroscience · doi:10.1037//0735-7044.99.4.691 · Cited by 55 · see citing works
Hart, S. J., Visootsak, J., Tamburri, P., Phuong, P., Baumer, N., Hernandez, M., Skotko, B. G., Ochoa‐Lubinoff, C., Liogier D'Ardhuy, X., Kishnani, P. S., et al. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38465 · Cited by 54 · see citing works
Characterization of the cardiac phenotype in neonatal Ts65Dn mice
Williams, A. D., Mjaatvedt, C. H., & Moore, C. S. (2007) · Developmental Dynamics · doi:10.1002/dvdy.21416 · Cited by 53 · see citing works
Genetic analysis of Down syndrome-associated heart defects in mice
Liu, C., Morishima, M., Yu, T., Matsui, S., Zhang, L., Fu, D., Pao, A., Costa, A. C. S., Gardiner, K., Cowell, J. K., et al. (2011) · Human Genetics · doi:10.1007/s00439-011-0980-2 · Cited by 51 · 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-citationStarbuck, J. M., Dutka, T., Ratliff, T. S., Reeves, R. H., & Richtsmeier, J. T. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36594 · Cited by 50 · see citing works
Self-citationModeling an Anti-Amyloid Combination Therapy for Alzheimer's Disease
Chow, V. W., Savonenko, A., Melnikova, T., Kim, H., Price, D., Li, T., & Wong, P. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000337 · Cited by 48 · see citing works
Self-citationLi, H., Edie, S., Klinedinst, D. K., Jeong, J. S., Blackshaw, S., Maslen, C. L., & Reeves, R. H. (2016) · Genetics · doi:10.1534/genetics.116.188045 · Cited by 45 · see citing works
Self-citationDissecting Alzheimer disease in Down syndrome using mouse models
Choong, X. Y., Tosh, J., Pulford, L. J., & Fisher, E. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00268 · Cited by 40 · see citing works
Humanized 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-citationHighly stable maintenance of a mouse artificial chromosome in human cells and mice
Kazuki, K., Takehara, S., Uno, N., Imaoka, N., Abe, S., Takiguchi, M., Hiramatsu, K., Oshimura, M., & Kazuki, Y. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.10.171 · 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-citationKolb, B. E., & Whishaw, I. Q. (1985) · Behavioral Neuroscience · doi:10.1037/0735-7044.99.4.691 · Cited by 35 · see citing works
Brain ventriculomegaly in Down syndrome mice is caused by Pcp4 dose-dependent cilia dysfunction.
Raveau, M., Nakahari, T., Asada, S., Ishihara, K., Amano, K., Shimohata, A., Sago, H., & Yamakawa, K. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx007 · Cited by 33 · see citing works
Nonaka, M., Fitzpatrick, R., Lapira, J., Wheeler, D. G., Spooner, P. A., Parada, M. C., Muñoz, M., Tully, T., Peters, M., & Morris, R. (2017) · European Journal of Neuroscience · doi:10.1111/ejn.13637 · Cited by 33 · see citing works
Centrosomes are multifunctional regulators of genome stability
Lerit, D. A., & Poulton, J. S. (2015) · Chromosome Research · doi:10.1007/s10577-015-9506-4 · Cited by 33 · see citing works
Hematopoietic disorders in Down syndrome.
Choi, J. K. (2008) · PubMed Central · Cited by 33 · see citing works
Morphological integration of soft-tissue facial morphology in down syndrome and siblings
Starbuck, J. M., Reeves, R. H., & Richtsmeier, J. T. (2011) · American Journal of Physical Anthropology · doi:10.1002/ajpa.21583 · Cited by 30 · see citing works
Self-citationCytogenetic Evaluation of Down Syndrome: A Review of 1020 Referral Cases
Chandra, N., Cyrus, C., Lakshminarayana, P., Nallasivam, P., Ramesh, A., Gopinath, P. M., & Marimuthu, K. M. (2010) · International Journal of Human Genetics · doi:10.1080/09723757.2010.11886090 · Cited by 29 · see citing works
Increased male reproductive success in Ts65Dn “Down syndrome” mice
Moore, C. S., Hawkins, C. E., Franca, A., Lawler, A. M., Devenney, B., Das, I., & Reeves, R. H. (2010) · Mammalian Genome · doi:10.1007/s00335-010-9300-8 · Cited by 24 · see citing works
Self-citationPolk, R. C., Gergics, P., Steimle, J. D., Li, H., Moskowitz, I. P. G., Camper, S. A., & Reeves, R. H. (2015) · BMC Developmental Biology · doi:10.1186/s12861-015-0080-y · Cited by 16 · see citing works
Self-citationDutka, T., Hallberg, D. L., & Reeves, R. H. (2014) · Mechanisms of Development · doi:10.1016/j.mod.2014.11.004 · Cited by 15 · see citing works
Self-citationHematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks
Wang, Y., Chang, J., Shao, L., Feng, W., Luo, Y., Chow, M., Du, W., Meng, A., & Zhou, D. (2016) · Radiation Research · doi:10.1667/rr14407.1 · Cited by 13 · see citing works
Brose, R. D., Savonenko, A. V., Devenney, B., Smith, K. D., & Reeves, R. H. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00096 · Cited by 11 · see citing works
Self-citationFernandez, F., & Reeves, R. H. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-16522-6_12 · Cited by 10 · see citing works
Self-citationSingh, N., Dutka, T., Reeves, R. H., & Richtsmeier, J. T. (2015) · Developmental Dynamics · doi:10.1002/dvdy.24361 · Cited by 9 · see citing works
Self-citationPrasher, V. P. (1995) · Down Syndrome Research and Practice · doi:10.3104/reports.45 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Besson V 2005 Studying dosage effects for human chromosome 21 homologous genes using chromosomal engineering in the mouse 19th International Mouse Genome Conference
Cited by
Sorted by citations
The brain and its time: intrinsic neural timescales are key for input processing
Golesorkhi, M., Gomez-Pilar, J., Zilio, F., Berberian, N., Wolff, A., Yagoub, M. C. E., & Northoff, G. (2021) · Communications Biology · doi:10.1038/s42003-021-02483-6 · Cited by 198 · see citing works
Aneuploidy as a promoter and suppressor of malignant growth
Vasudevan, A., Schukken, K. M., Sausville, E. L., Girish, V., Adebambo, O. A., & Sheltzer, J. M. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-020-00321-1 · Cited by 176 · see citing works
Telomere Replication: Solving Multiple End Replication Problems
Bonnell, E., Pasquier, E., & Wellinger, R. J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.668171 · Cited by 89 · see citing works
Access to antivenoms in the developing world: A multidisciplinary analysis
Potet, J., Beran, D., Ray, N., Alcoba, G., Habib, A. G., Iliyasu, G., Waldmann, B., Ralph, R., Faiz, M. A., Monteiro, W. M., et al. (2021) · Toxicon X · doi:10.1016/j.toxcx.2021.100086 · Cited by 103 · see citing works
Ts66Yah, a mouse model of down syndrome with improved construct and face validity
Duchon, A., del Mar Muñiz Moreno, M., Chevalier, C., Nalesso, V., Andre, P., Fructuoso-Castellar, M., Mondino, M., Po, C., Noblet, V., Birling, M.-C., et al. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049721 · Cited by 58 · see citing works
Chen, X., Salehi, A., Pearn, M. L., Overk, C., Nguyen, P. D., Kleschevnikov, A. M., Maccecchini, M. L., & Mobley, W. C. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12185 · Cited by 54 · see citing works
Impact of increased <i>APP</i> gene dose in Down syndrome and the Dp16 mouse model
Sawa, M., Overk, C., Becker, A., Derse, D., Albay, R., Weldy, K., Salehi, A., Beach, T. G., Doran, E., Head, E., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12463 · Cited by 54 · see citing works
All 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-citationNeurodevelopment 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
“MAC21, though not well characterized, appears to have an increase in brain volume, the opposite of what is observed in humans.”
MethodInfluentialShaw, 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
“It will be important to design careful genetic management procedures and standardized protocols for analysis of the newer models arriving in the DS research space, including the MAC21 and Ts66Yah mice (Kazuki et al., 2020; Birling et al., 2017).”
MethodAskary, A., Chen, W., Choi, J., Du, L. Y., Elowitz, M. B., Gagnon, J. A., Schier, A. F., Seidel, S., Shendure, J., Stadler, T., et al. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00788-w · Cited by 39 · see citing works
“…magnitude, spatial transcriptomic methods to advance to a level at which entire animals can be routinely profiled at single-cell resolution, or DNA-based recording to advance to the point where the entire, longitudinal history of a cell can be captured by a single, contiguous DNA sequencing read.”
Pecze, L., Randi, E. B., & Szabó, C. (2020) · Molecular Medicine · doi:10.1186/s10020-020-00225-8 · Cited by 41 · see citing works
“There are also mouse models overexpressing the human chromosome 21, or part of it (O’Doherty et al. 2005; Miyamoto et al. 2014; Kazuki et al. 2020); while these animals have the ‘correct’ extra genes, these are human genes encoding human proteins: the interaction of these human proteins with the mouse proteins is like…”
BackgroundA transchromosomic rat model with human chromosome 21 shows robust down syndrome features.
Kazuki, Y., Gao, F. J., Yamakawa, M., Hirabayashi, M., Kazuki, K., Kajitani, N., Miyagawa-Tomita, S., Abe, S., Sanbo, M., Hara, H., et al. (2022) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.12.015 · Cited by 41 · see citing works
Self-citationPradier, B., Wachsmuth, L., Nagelmann, N., Segelcke, D., Kreitz, S., Heß, A., Pogatzki-Zahn, E. M., & Faber, C. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118626 · Cited by 38 · see citing works
Murray, A., Gough, G., Cindrić, A., Vučković, F., Koschut, D., Borelli, V., Petrović, D. J., Bekavac, A., Plećaš, A., Hribljan, V., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104692 · Cited by 37 · see citing works
Lana-Elola, E., Cater, H., Watson-Scales, S., Greenaway, S., Müller-Winkler, J., Gibbins, D., Nemes, M., Slender, A., Hough, T., Keskivali-Bond, P., et al. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.049157 · Cited by 35 · see citing works
Chi, C., Knight, W. E., Riching, A. S., Zhang, Z., Tatavosian, R., Zhuang, Y., Moldovan, R., Rachubinski, A. L., Gao, D., Xu, H., et al. (2023) · iScience · doi:10.1016/j.isci.2023.107012 · Cited by 30 · see citing works
Sierra, C., Sabariego-Navarro, M., Fernández‐Blanco, Á., Cruciani, S., Zamora‐Moratalla, A., Novoa, E. M., & Dierssen, M. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02440-9 · Cited by 29 · see citing works
“The study was conducted according to the guidelines of the local (law 32/2007) and European regulations (2010/63/EU) and the Standards for Use of Laboratory Animals no.”
The Underlying Relationship between Keratoconus and Down Syndrome
Akoto, T., Li, J. J., Estes, A. J., Karamichos, D., & Liu, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810796 · Cited by 31 · see citing works
Dysregulated systemic metabolism in a Down syndrome mouse model
Sarver, D. C., Xu, C., Vélez, L. M., Aja, S. M., Jaffe, A. E., Seldin, M. M., Reeves, R. H., & Wong, G. W. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101666 · Cited by 31 · see citing works
Self-citationAβ 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
Brain circuit pathology in Down syndrome: from neurons to neural networks
Bartesaghi, R. (2023) · Reviews in the Neurosciences · doi:10.1515/revneuro-2022-0067 · Cited by 25 · see citing works
Asynchronous excitatory neuron development in an isogenic cortical spheroid model of Down syndrome
Li, Z., Klein, J. A., Rampam, S., Kurzion, R., Campbell, N. B., Patel, Y., Haydar, T. F., & Zeldich, E. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.932384 · Cited by 24 · see citing works
Mouse models of aneuploidy to understand chromosome disorders
Tosh, J., Tybulewicz, V., & Fisher, E. M. C. (2022) · Mammalian Genome · doi:10.1007/s00335-021-09930-z · Cited by 24 · see citing works
Xing, Z., Li, Y., Cortes-Gomez, E., Jiang, X., Gao, S., Pao, A., Shan, J., Song, Y., Perez, A., Yu, T., et al. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad056 · Cited by 23 · see citing works
Self-citationAnand, A., Chatterjee, B., Dhiman, A., Goel, R., Khan, E., Malhotra, A., Santra, V., Salvi, N. C., Khadilkar, M. V., Bhatnagar, I., et al. (2021) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2021.113523 · Cited by 23 · see citing works
Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches
Farrell, C., Mumford, P., & Wiseman, F. K. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.909669 · Cited by 22 · 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-citationDiverse identities and sites of action of cochlear neurotransmitters
Kitcher, S. R., Pederson, A., & Weisz, C. J. C. (2021) · Hearing Research · doi:10.1016/j.heares.2021.108278 · Cited by 18 · see citing works
Cell models for Down syndrome-Alzheimer’s disease research
Wu, Y., West, N. R., Bhattacharyya, A., & Wiseman, F. K. (2022) · Neuronal Signaling · doi:10.1042/ns20210054 · Cited by 17 · see citing works
Moyer, A. J., Fernandez, F., Li, Y., Klinedinst, D. K., Florea, L., Kazuki, Y., Oshimura, M., & Reeves, R. H. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.049712 · Cited by 17 · see citing works
Self-citationCardiovascular Physiology and Pathophysiology in Down Syndrome
Cılhoroz, B., Receno, C. N., Heffernan, K. S., & DeRuisseau, L. R. (2022) · Physiological Research · doi:10.33549/physiolres.934791 · Cited by 16 · see citing works
“6% of animals had a structural defect of the heart [85], suggesting it”
BackgroundInfluentialBartesaghi, R., Vicari, S., & Mobley, W. C. (2022) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-041521-103641 · Cited by 15 · see citing works
Behavioral Phenotyping for Down Syndrome in Mice
Roper, R. J., Goodlett, C., de Lagrán, M. M., & Dierssen, M. (2020) · Current Protocols in Mouse Biology · doi:10.1002/cpmo.79 · Cited by 10 · see citing works
“A new transchromosomal model has been made that contains ∼93% of Hsa21q (Kazuki et al., 2020).”
MethodBiphasic cell cycle defect causes impaired neurogenesis in down syndrome
Sharma, V., Nehra, S., Do, L. H., Ghosh, A., Deshpande, A. J., & Singhal, N. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1007519 · Cited by 14 · see citing works
“In addition to the development of newer mouse models (Kazuki et al., 2020), human-induced pluripotent stem cells (hiPSCs) (Takahashi and Yamanaka, 2006) (Takahashi et al.”
BackgroundModeling specific aneuploidies: from karyotype manipulations to biological insights
Truong, M. A., Cané‐Gasull, P., & Lens, S. M. A. (2023) · Chromosome Research · doi:10.1007/s10577-023-09735-7 · Cited by 15 · see citing works
“These included the generation of mouse models for Down syndrome by transferring either a large part of human chr21 (Shinohara et al. 2001; O’Doherty et al. 2005), or a mouse artificial cho-mosome containing the q-arm of the human chr21, into mouse embryonic stem cells (ESCs) (Kazuki et al. 2020).”
BackgroundInsights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer
Carey-Smith, S. L., Kotecha, R. S., Cheung, L. C., & Malinge, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25136815 · Cited by 17 · see citing works
“This includes transgenic models triplicated for Mm10, Mm16 and Mm17 [171], as well as the Tc1 and TcMAC21 models, which were developed using microcell mediated chromosome transfer [172], that span 70–75% of the protein-coding Hsa21 genes [173,174].”
MethodA clinical-translational review of sleep problems in neurodevelopmental disabilities
Peters, S. U., Shelton, A. R., Malow, B. A., & Neul, J. L. (2024) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-024-09559-4 · Cited by 14 · see citing works
“These mice have many of the same phenotypic features of DS that are evident in humans, including a distinct facial structure, a greater prevalence for congenital heart defects, a smaller-than-usual cerebellum and learning difficulties [90].”
BackgroundGao, 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-citationVuong, C. K., Weber, A., Seong, P., Matoba, N., Chen, Y.-J., Peyer, J., Younesi, S., Salinda, A., Gomez, D., Rivas, G., et al. (2026) · Science · doi:10.1126/science.aea1259 · Cited by 14 · see citing works
Rethinking nomenclature for interspecies cell fusions
Pavlovic, B. J., Fox, D., Schaefer, N. K., & Pollen, A. A. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00447-4 · Cited by 13 · see citing works
Watson, L. A., & Meharena, H. S. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1198129 · Cited by 13 · see citing works
“Initial characterization of the TcMAC21 mouse indicates reduced cerebellar volume and behavioral changes consistent with those observed in previous mouse models of DS (Kazuki et al., 2020).”
BackgroundResultDown syndrome and leukemia: An insight into the disease biology and current treatment options
Barwe, S. P., Kolb, E. A., & Gopalakrishnapillai, A. (2023) · Blood Reviews · doi:10.1016/j.blre.2023.101154 · 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
Low bone mass and impaired fracture healing in mouse models of Trisomy21 (Down syndrome)
Sherman, K. M., Williams, D. K., Welsh, C. A., Cooper, A., Falck, A. R., Huggins, S. S., Bokhari, R. S., Gaddy, D., McKelvey, K. D., Dawson, L., et al. (2022) · Bone · doi:10.1016/j.bone.2022.116471 · Cited by 13 · 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-citationNeocortical neuronal production and maturation defects in the TcMAC21 mouse model of Down syndrome
Kurabayashi, N., Fujii, K., Otobe, Y., Hiroki, S., Hiratsuka, M., Yoshitane, H., Kazuki, Y., & Takao, K. (2023) · iScience · doi:10.1016/j.isci.2023.108379 · Cited by 13 · see citing works
Self-citationShaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain
Farley, S. J., Grishok, A., & Zeldich, E. (2022) · Epigenetics & Chromatin · doi:10.1186/s13072-022-00471-6 · Cited by 13 · see citing works
Shao, L., Gao, F., Chinnasamy, V., Kazuki, Y., Oshimura, M., Reeves, R. H., & Stafstrom, C. E. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106198 · Cited by 12 · see citing works
Self-citationAbe, S., Honma, K., Okada, A., Kazuki, K., Tanaka, H., Endo, T., Morimoto, K., Moriwaki, T., Hamamichi, S., Nakayama, Y., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-99535-y · Cited by 11 · see citing works
Self-citationDierssen, M., Hérault, Y., Helguera, P. R., de Lagrán, M. M., Vázquez, A. V., Christian, B. T., Carmona‐Iragui, M., Wiseman, F. K., Mobley, W. C., Fisher, E., et al. (2021) · Molecular Syndromology · doi:10.1159/000514437 · Cited by 11 · see citing works
Simulating PIP2-Induced Gating Transitions in Kir6.2 Channels
Bründl, M., Pellikan, S., & Stary‐Weinzinger, A. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.711975 · Cited by 11 · see citing works
Genetics and etiology of congenital heart disease
Narayan, P., Richter, F., & Morton, S. U. (2024) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2024.01.009 · Cited by 10 · see citing works
Hiramuki, Y., Hosokawa, M., Osawa, K., Shirakawa, T., Watanabe, Y., Hanajima, R., Kugoh, H., Awano, H., Matsuo, M., & Kazuki, Y. (2025) · Scientific Reports · doi:10.1038/s41598-025-85369-5 · Cited by 10 · see citing works
“Using mouse artificial chromosome, Down syndrome model mice carrying the long arm of human chromosome 21 27 , human antibody-producing mice carrying human immunoglobulin loci 28 , and human drug-metabolizing enzyme-producing rats carrying UGT2 cluster and CYP3A cluster 29 have been developed.”
Self-citationUltrasonic 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
Šemberová, K., Svitok, M., Marhold, K., Suda, J., & Schmickl, R. (2021) · Annals of Botany · doi:10.1093/aob/mcab123 · Cited by 9 · see citing works
Li, Y., Xing, Z., Yu, T., Pao, A., Daadi, M. M., & Yu, Y. E. (2021) · Genes · doi:10.3390/genes12081215 · Cited by 9 · see citing works
“The second group of genomic mouse models developed were transchromosomal models [11,12].”
BackgroundInfluentialSelf-citationMiyamoto, H., Kobayashi, H., Kishima, N., Yamazaki, K., Hamamichi, S., Uno, N., Abe, S., Hiramuki, Y., Kazuki, K., Tomizuka, K., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1218 · Cited by 8 · see citing works
“…mouse artificial chromosomes (MACs) have achieved the delivery of up to 24 Mb human chromosome fragment (hCF) into mice with stable intra-individual retention and germline transmission, cumulating in generation of hCF containing animal models termed tran-schromosomic (TC) animals ( 3 , 7 , 8 ).”
BackgroundMethodSelf-citationLlambrich, S., González, R., Wouters, J., Muñoz, J. R., Salassa, S., Wouters, K., Bulck, V. V., Sharpe, J. A., Callaerts‐Vegh, Z., Velde, G. V., et al. (2022) · Nutrients · doi:10.3390/nu14194167 · Cited by 8 · see citing works
“Our results replicated previous findings on the face, skull, and mandible morphology in newborn and adult Ts65Dn mice [3,56,57] and were consistent with the craniofacial malformations identified in other models of DS, such as TcMAC21 [58] and Dp1Tyb mice [59,60].”
ResultAraya, P., Niemeyer, B., Schade, K., Dunn, L. N., Waugh, K., Busquet, N., Brindley, C., Brown, C., Winkler, C., Lyford, H. R., et al. (2025) · iScience · doi:10.1016/j.isci.2025.113130 · Cited by 7 · see citing works
Infantile epileptic spasms syndrome: Mechanisms and therapeutic approaches
Stafstrom, C. E. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00822 · Cited by 7 · see citing works
“A newer model, transchromosomic mouse artificial chromosome 21 (TcMAC21), carries a copy of human chromosome 21 and therefore harbors a genetic composition very similar to human DS [137].”
Loss of GDE2 leads to complex behavioral changes including memory impairment
Daudelin, D., Westerhaus, A., Zhang, N., Leyder, E. C., Savonenko, A. V., & Sockanathan, S. (2024) · Behavioral and Brain Functions · doi:10.1186/s12993-024-00234-1 · Cited by 8 · see citing works
“These types of probe trials were used in numerous previous studies of cognitive deficits in different mouse and rat models of Alzheimer’s and other diseases [23, 27–29].”
MethodSelf-citationAhmed, M. M., Block, A., Busquet, N., & Gardiner, K. (2021) · Genes · doi:10.3390/genes12101528 · Cited by 7 · see citing works
“There are technical challenges to generating complete trisomy, and while many partial trisomies have been created (reviewed in [21,24–27]), a full trisomy model has only recently been produced [28].”
BackgroundUno, N., Satofuka, H., Miyamoto, H., Honma, K., Suzuki, T., Yamazaki, K., Ito, R., Moriwaki, T., Hamamichi, S., Tomizuka, K., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.07.002 · Cited by 6 · see citing works
“The assessment of chromosome damage is an essential consideration; however, a comprehensive study such as quantitative nextgeneration sequencing-based telomere-to-telomere assembly(39) is needed to evaluate the efficiency of transferring intact, complete chromosomes to detect chromosomal damage that is not identifiabl…”
Self-citationThe Hallmarks of Aneuploidy in Cancer and Congenital Syndromes
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
“In 2020, scientists introduced TcMAC21, a trans-chromosomic mouse model of DS that contains the human chromosome 21q arm (94).”
Self-citationIncreased seizure susceptibility and neocortical excitability in TcMAC21 Down syndrome mice
Chinnasamy, V., Stafstrom, C. E., & Shao, L. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.09.016 · Cited by 5 · see citing works
Tenreiro, M. F., & Muotri, A. R. (2026) · Developmental Cell · doi:10.1016/j.devcel.2026.02.018 · Cited by 6 · see citing works
Raza, 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
“Hsa21 is syntenic with regions on Mmu 16, 10, and 17, containing ∼ 105, 37, and 19 protein-coding genes 20 respectively, not including unrelated keratin-associated genes.”
InfluentialSelf-citationScott-McKean, J. J., Jones, R., Johnson, M. W., Mier, J., Basten, I. A., Stasko, M. R., & Costa, A. C. S. (2023) · Brain Sciences · doi:10.3390/brainsci13050743 · Cited by 5 · see citing works
“The MAC was introduced stably into embryonic stem cells which were then used to produce this mouse model [39].”
MethodBardhan, S., Li, H., Tarver, E. D., Schramm, C. A., Brown, M. K., Garcia, L., Schwartz, B. N., Mazzucco, A., Natarajan, N., Walsh, E., et al. (2024) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.32081 · Cited by 5 · see citing works
Microcell-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
“Recently, Reeves and colleagues developed a mouse model of DS called TcMAC21 that is genetically engineered to carry a copy of Hsa21 [82].”
TcMAC21 mouse model recapitulates abnormal vascular physiology observed in humans with Down syndrome
Zheng, X., Sabouri, M., Irwin, B. J., Bernardo, J., & Machin, D. R. (2025) · Physiological Reports · doi:10.14814/phy2.70384 · Cited by 5 · see citing works
“The TcMAC21 mouse recapitulates many DS phenotypes, including congenital heart anomalies, developmental delays, and cognitive impairments (Kazuki et al., 2020).”
InfluentialLlambrich, 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
Shao, L., & Stafstrom, C. E. (2025) · Epilepsy Research · doi:10.1016/j.eplepsyres.2025.107686 · Cited by 4 · see citing works
Alldred, M. J., Pidikiti, H., Ibrahim, K. W., Lee, S. H., Heguy, A., Chiosis, G., Mufson, E. J., Stutzmann, G. E., & Ginsberg, S. D. (2025) · Biomolecules · doi:10.3390/biom15081131 · Cited by 3 · see citing works
“Alternative animal models of DS/AD could be considered, such as TcMac21 [102], encodes a triplicated copy of the entire human HSA21 chromosome in mice to confirm validity of targets and to identify potential novel targets not present in this initial analysis.”
Vertebrate and Invertebrate Animal Models for the Study of Down Syndrome
Granholm, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26168092 · Cited by 3 · see citing works
“The TcMAC21 mouse model of DS was first described in 2020 by Kazuki, Gao, and Reeves et al. [82].”
InfluentialSleep Fragmentation in TcMAC21 Mouse Model of Down Syndrome
Tusk, J., Canas, M. A. S., Haydar, T. F., & Dean, T. (2025) · Nature and Science of Sleep · doi:10.2147/nss.s545188 · Cited by 3 · see citing works
“Of note, the TcMAC21 mice did bear distinguishable physical characteristics noted previously, 13 including abnormal facies and shortened ears, making blinding investigators to mouse genotype impossible as the investigators interacting with the mice were the same as those collecting and analyzing…”
Stander, R. M. H., Ayyappan, N., Sikorski, D., van der Heijden, M. E., & Hsiao, K. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03744-2 · Cited by 4 · see citing works
“In multi-fi ber photometry experiments, we utilized a red fl uorescent calcium sensor protein [35] to contrast the peri-centromeric GFP on the HSA21q-MAC [25] to independently record neural calcium activity by spectral separation.”
Rataj-Baniowska, M., Mumford, P., Prestia, F., Stephan, P., Beament, M., Birling, M., Lanzillotta, C., Ciafardini, L., Barone, E., Lau, G., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71498 · Cited by 3 · see citing works
Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation
Chang, P., Pérez-González, M., Constable, J., Bush, D., Cleverley, K., Tybulewicz, V. L. J., Fisher, E., & Walker, M. C. (2024) · The Neuroscientist · doi:10.1177/10738584241271414 · Cited by 3 · see citing works
“TcMAC21 was then developed to improve upon this and also contains a freely segregating copy of Hsa21 but with ~93% of protein-coding genes and no detectable mosaicism (Kazuki and others 2020; see Fig.”
Yamazaki, K., Matsuo, K., Okada, A., Uno, N., Suzuki, T., Abe, S., Hamamichi, S., Kishima, N., Togai, S., Tomizuka, K., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-25959-9 · Cited by 3 · see citing works
Self-citationAlldred, M. J., Ibrahim, K. W., Pidikiti, H., Lee, S. H., Heguy, A., Chiosis, G., Mufson, E. J., Stutzmann, G. E., & Ginsberg, S. D. (2025) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2025.1546375 · Cited by 4 · see citing works
Minter, R., & Gardiner, K. (2021) · Genes · doi:10.3390/genes12111697 · Cited by 3 · see citing works
“Few comparisons of results here can be made with learning/memory deficits seen in other mouse models of DS for two reasons: (i) no other models have been assessed for performance in the puzzle box, double-H maze, or acoustic startle/prepulse inhibition, and (ii) female mice have been assessed in only a single DS model…”
ResultA 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
Seeking clarity on sex differences in cardiovascular complications of Down syndrome
Lam, M. P. Y. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00210.2023 · Cited by 3 · see citing works
Atak, Z., Srivastava, A., Gandhi, S., Park, E., Williams, J., Torii, M., & Haydar, T. F. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.0040-25.2025 · Cited by 2 · see citing works
Comparative analysis of craniofacial shape in two mouse models of Down syndrome: Ts65Dn and TcMAC21
Singh, N., Richtsmeier, J. T., & Reeves, R. H. (2024) · Journal of Anatomy · doi:10.1111/joa.14012 · Cited by 2 · see citing works
“…were bred, cared for, euthanized, and imaged according to the guidelines of the National Institute of Health and RIKEN Guide for the Care and Use of Laboratory Animals as well as the Institutional Animal Care and Use Committee protocols of the local universities involved (Kazuki et al., 2020).”
BackgroundMethodInfluentialSelf-citationIn preprints: insights into human heart development and congenital heart defects
Kathiriya, I. S. (2024) · Development · doi:10.1242/dev.204302 · Cited by 2 · see citing works
Kishima, N., Moriwaki, T., Uno, N., Suzuki, T., Abe, S., Sugawara, M., Nagashima, Y., Kazuki, K., Endo, T., Yamazaki, K., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-13138-5 · Cited by 2 · see citing works
“The following target DNA: probe combinations were utilized as previously described 9 : mouse DNA: mouse Cot-1 (Invitrogen/Thermo Fisher Scientific), human DNA: human Cot-1 (Invitrogen/Thermo Fisher Scientific), HLA-A :CH501-309N1, HLA-B /C: CH501-248L24, h B2M :RP11-292P13, and mouse minor…”
Self-citationDown syndrome: a model for chromosome abnormalities
Overk, C., & Mobley, W. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85654-6.00007-1 · Cited by 2 · see citing works
Guedj, F., Kane, E., Bishop, L. A., Pennings, J. L. A., Hérault, Y., & Bianchi, D. W. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.23.509067 · Cited by 2 · see citing works
“Unfortunately this is not yet the case with the new TcMAC21 mouse model due to deletion in human chromosome 21 that occurred during generation of this strain (75).”
BackgroundSingh, N., Reeves, R. H., & Richtsmeier, J. T. (2025) · Journal of Anatomy · doi:10.1111/joa.70066 · Cited by 1 · see citing works
“TcHSA21rats were maintained on a Wistar (Crlj:Wj, Charles River) and the TcMAC21 mice were on a BDF1 (C57BL/6 L (B6)xDBA/2 J(D2)) background (Kazuki et al., 2020; Kazuki et al., 2022).”
InfluentialSelf-citationGene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model
Chen, F., Saqib, M., Nguyen, C. M., Sarver, D. C., Yu, Y. E., Aja, S. M., Seldin, M. M., & Wong, G. W. (2026) · eLife · doi:10.7554/elife.110476.3 · Cited by 1 · see citing works
Mammalian genome research resources available from the National BioResource Project in Japan
Mizuno‐Iijima, S., Kawamoto, S., Asano, M., Mashimo, T., Wakana, S., Nakamura, K., Nishijima, K.-I., Okamoto, H., Saito, K., Yoshina, S., et al. (2024) · Mammalian Genome · doi:10.1007/s00335-024-10063-2 · 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
“These genetic alterations do not fully represent DS’s aneuploidy and other mouse and rat models have been developed recently that more faithfully represent the trisomic nature of DS ( Kazuki et al., 2020 ; Kazuki et al., 2022 ).”
BackgroundGene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse modelPreprint
Chen, F., Saqib, M., Nguyen, C. M., Sarver, D. C., Yu, Y. E., Aja, S. M., Seldin, M. M., & Wong, G. W. (2026) · eLife · doi:10.7554/elife.110476 · Cited by 1 · see citing works
“TcMAC21 is a recently generated transchromosomic mouse model carrying a non-mosaic Hsa21q ( Kazuki et al., 2020 ).”
The first transchromosomic rat model with human chromosome 21 shows robust Down syndrome featuresPreprint
Kazuki, Y., Gao, F., Yamakawa, M. Y., Hirabayashi, M., Kazuki, K., Kajitani, N., Miyagawa‐Tomita, S., Abe, S., Sanbo, M., Hara, H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.03.462958
Self-citationA Mouse Model with Complete Penetrance for Atrioventricular Septal Defect/Complete AV CanalPreprint
Li, Y., Andersen, P., Liu, X., Moyer, A. J., Kwon, C., & Reeves, R. H. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.03.478994
Self-citationIn vivo and in vitro models for research on Down syndrome
Ganguly, B. B. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90456-8.00013-2 · Cited by 1 · see citing works
- Authors
- Kazuki, Y., Gao, F. J., Li, Y., Moyer, A. J., Devenney, B., Hiramatsu, K., Miyagawa-Tomita, S., Abe, S., Kazuki, K., Kajitani, N., Uno, N., Takehara, S., Takiguchi, M., Yamakawa, M., Hasegawa, A., Shimizu, R., Matsukura, S., Noda, N., Ogonuki, N., Inoue, K., Matoba, S., Ogura, A., Florea, L. D., Savonenko, A., Xiao, M., Wu, D., Batista, D. A., Yang, J., Qiu, Z., Singh, N., Richtsmeier, J. T., Takeuchi, T., Oshimura, M., & Reeves, R. H.
- Affiliations
- Chromosome Engineering Research Center (JP)
- Johns Hopkins University (US)
- Tottori University (JP)
- Department of Animal Nursing Science, Yamazaki University of Animal Health Technology, Hachioji, Tokyo, Japan
- Tohoku University (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- RIKEN BioResource Research Center (JP)
- Department of Neuroscience, John Hopkins University School of Medicine, Baltimore, United States
- Zhejiang University (CN)
- Pennsylvania State University (US)
- California State University, Sacramento (US)
- Corresponding author
- Kazuki, Yasuhiro
- Reeves, Roger H
- ORCID
- Kazuki, Yasuhiro
- Gao, Feng J
- Li, Yicong
- Moyer, Anna J
- Devenney, Benjamin
- Abe, Satoshi
- Kazuki, Kanako
- Uno, Narumi
- Yamakawa, Miho
- Hasegawa, Atsushi
- Shimizu, Ritsuko
- Matsukura, Satoko
- Noda, Naohiro
- Inoue, Kimiko
- Matoba, Shogo
- Ogura, Atsuo
- Florea, Liliana D
- Savonenko, Alena
- Wu, Dan
- Batista, Denise AS
- Yang, Junhua
- Qiu, Zhaozhu
- Singh, Nandini
- Richtsmeier, Joan T
- Takeuchi, Takashi
- Reeves, Roger H
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2020-06-29
- Volume
- 9
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7358007
- OpenAlex
- W3037987616
- Cited by
- 125
- References
- 77
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 18 · 2023: 19 · 2022: 23 · 2021: 22 · 2020: 6
- FWCI
- 14.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD098540-01, R01HD038384)
- Japan Society for the Promotion of Science (25221308)
- Core Research for Evolutional Science and Technology (JPMJCR18S4)
- 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, artificial chromosomes, microcell-mediated chromosome transfer, cardiac anomalies, craniofacial anomalies, brain anomalies, learning and memory impairment, synaptic plasticity, gene expression
- MeSH terms
- Whole Genome Sequencing, Animals, Brain, Chromosomes, Human, Pair 21, Disease Models, Animal, Down Syndrome, Female, Heart Defects, Congenital, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Trisomy, Mice
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
