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A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
eLife Sciences Publications, Ltd
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358007/ https://www.ncbi.nlm.nih.gov/pubmed/32597754 http://dx.doi.org/10.7554/eLife.56223 |
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| author | Kazuki, Yasuhiro Gao, Feng J Li, Yicong Moyer, Anna J Devenney, Benjamin Hiramatsu, Kei Miyagawa-Tomita, Sachiko Abe, Satoshi Kazuki, Kanako Kajitani, Naoyo Uno, Narumi Takehara, Shoko Takiguchi, Masato Yamakawa, Miho Hasegawa, Atsushi Shimizu, Ritsuko Matsukura, Satoko Noda, Naohiro Ogonuki, Narumi Inoue, Kimiko Matoba, Shogo Ogura, Atsuo Florea, Liliana D Savonenko, Alena Xiao, Meifang Wu, Dan Batista, Denise AS Yang, Junhua Qiu, Zhaozhu Singh, Nandini Richtsmeier, Joan T Takeuchi, Takashi Oshimura, Mitsuo Reeves, Roger H |
| author_facet | Kazuki, Yasuhiro Gao, Feng J Li, Yicong Moyer, Anna J Devenney, Benjamin Hiramatsu, Kei Miyagawa-Tomita, Sachiko Abe, Satoshi Kazuki, Kanako Kajitani, Naoyo Uno, Narumi Takehara, Shoko Takiguchi, Masato Yamakawa, Miho Hasegawa, Atsushi Shimizu, Ritsuko Matsukura, Satoko Noda, Naohiro Ogonuki, Narumi Inoue, Kimiko Matoba, Shogo Ogura, Atsuo Florea, Liliana D Savonenko, Alena Xiao, Meifang Wu, Dan Batista, Denise AS Yang, Junhua Qiu, Zhaozhu Singh, Nandini Richtsmeier, Joan T Takeuchi, Takashi Oshimura, Mitsuo Reeves, Roger H |
| author_sort | Kazuki, Yasuhiro |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7358007 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-73580072020-07-15 A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21 Kazuki, Yasuhiro Gao, Feng J Li, Yicong Moyer, Anna J Devenney, Benjamin Hiramatsu, Kei Miyagawa-Tomita, Sachiko Abe, Satoshi Kazuki, Kanako Kajitani, Naoyo Uno, Narumi Takehara, Shoko Takiguchi, Masato Yamakawa, Miho Hasegawa, Atsushi Shimizu, Ritsuko Matsukura, Satoko Noda, Naohiro Ogonuki, Narumi Inoue, Kimiko Matoba, Shogo Ogura, Atsuo Florea, Liliana D Savonenko, Alena Xiao, Meifang Wu, Dan Batista, Denise AS Yang, Junhua Qiu, Zhaozhu Singh, Nandini Richtsmeier, Joan T Takeuchi, Takashi Oshimura, Mitsuo Reeves, Roger H eLife Genetics and Genomics 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. eLife Sciences Publications, Ltd 2020-06-29 /pmc/articles/PMC7358007/ /pubmed/32597754 http://dx.doi.org/10.7554/eLife.56223 Text en © 2020, Kazuki et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
| spellingShingle | Genetics and Genomics Kazuki, Yasuhiro Gao, Feng J Li, Yicong Moyer, Anna J Devenney, Benjamin Hiramatsu, Kei Miyagawa-Tomita, Sachiko Abe, Satoshi Kazuki, Kanako Kajitani, Naoyo Uno, Narumi Takehara, Shoko Takiguchi, Masato Yamakawa, Miho Hasegawa, Atsushi Shimizu, Ritsuko Matsukura, Satoko Noda, Naohiro Ogonuki, Narumi Inoue, Kimiko Matoba, Shogo Ogura, Atsuo Florea, Liliana D Savonenko, Alena Xiao, Meifang Wu, Dan Batista, Denise AS Yang, Junhua Qiu, Zhaozhu Singh, Nandini Richtsmeier, Joan T Takeuchi, Takashi Oshimura, Mitsuo Reeves, Roger H A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21 |
| title | A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21 |
| title_full | A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21 |
| title_fullStr | A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21 |
| title_full_unstemmed | A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21 |
| title_short | A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21 |
| title_sort | non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21 |
| topic | Genetics and Genomics |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358007/ https://www.ncbi.nlm.nih.gov/pubmed/32597754 http://dx.doi.org/10.7554/eLife.56223 |
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