RRC ID 63376
Author Kazuki Y, Gao FJ, Li Y, Moyer AJ, 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 LD, Savonenko A, Xiao M, Wu D, Batista DA, Yang J, Qiu Z, Singh N, Richtsmeier JT, Takeuchi T, Oshimura M, Reeves RH.
Title A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21.
Journal Elife
Abstract 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.
Volume 9
Published 2020-6-29
DOI 10.7554/eLife.56223
PII 56223
PMID 32597754
PMC PMC7358007
MeSH Animals Brain / pathology Chromosomes, Human, Pair 21 / genetics* Disease Models, Animal Down Syndrome / genetics* Female Heart Defects, Congenital / genetics Humans Male Mice Mice, Inbred C57BL Mice, Transgenic / genetics* Trisomy / genetics Whole Genome Sequencing
IF 7.08
Mice RBRC05796