A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21.

Autor:	Kazuki Y; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan.; Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan., Gao FJ; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States., Li Y; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States., Moyer AJ; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States.; Department of Genetic Medicine, John Hopkins University School of Medicine, Baltimore, United States., Devenney B; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States., Hiramatsu K; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan., Miyagawa-Tomita S; Department of Animal Nursing Science, Yamazaki University of Animal Health Technology, Hachioji, Tokyo, Japan.; Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Abe S; Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan., Kazuki K; Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan., Kajitani N; Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan., Uno N; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan., Takehara S; Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan., Takiguchi M; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan., Yamakawa M; Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan., Hasegawa A; Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan., Shimizu R; Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan., Matsukura S; Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan., Noda N; Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan., Ogonuki N; Bioresource Engineering Division, RIKEN BioResource Research Center (BRC), Tsukuba, Japan., Inoue K; Bioresource Engineering Division, RIKEN BioResource Research Center (BRC), Tsukuba, Japan., Matoba S; Bioresource Engineering Division, RIKEN BioResource Research Center (BRC), Tsukuba, Japan., Ogura A; Bioresource Engineering Division, RIKEN BioResource Research Center (BRC), Tsukuba, Japan., Florea LD; Department of Genetic Medicine, John Hopkins University School of Medicine, Baltimore, United States., Savonenko A; Departments of Pathology and Neurology, John Hopkins University School of Medicine, Baltimore, United States., Xiao M; Department of Neuroscience, John Hopkins University School of Medicine, Baltimore, United States., Wu D; Department of Biomedical Engineering, Zhejiang University, Hangzhou, China., Batista DA; Department of Pathology, John Hopkins University School of Medicine, Baltimore, United States., Yang J; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States., Qiu Z; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States., Singh N; Department of Anthropology, Penn State University, State College, United States., Richtsmeier JT; Division of Biosignaling, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, Japan., Takeuchi T; Department of Anthropology, California State University, Sacramento, United States., Oshimura M; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan., Reeves RH; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States.; Department of Genetic Medicine, John Hopkins University School of Medicine, Baltimore, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Jun 29; Vol. 9. Date of Electronic Publication: 2020 Jun 29.
DOI:	10.7554/eLife.56223
Abstrakt:	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. Competing Interests: YK, FG, YL, AM, BD, KH, SM, SA, KK, NK, NU, ST, MT, MY, AH, RS, SM, NN, NO, KI, SM, AO, LF, AS, MX, DW, DB, JY, ZQ, NS, JR, TT, MO, RR No competing interests declared (© 2020, Kazuki et al.)
Databáze:	MEDLINE
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