A Researcher’s guide to rodent models of Down syndrome: Recent insights and translational perspectives
Rodent models of Down syndrome (DS) have been transformative in identifying basic mechanisms underlying the effects of Trisomy 21 at the molecular, cellular, physiological, and neurobehavioral levels. Each model, with its unique genomic architecture, has advanced our understanding of the complex multisystem etiology of DS. The availability of multiple models necessitates the challenge of selecting appropriate models to address a particular scientific question, experimental design, and translational relevance. This primer guides the reader through the various rodent models of DS and the genomic and phenotypic effects they recapitulate. We also provide recommendations and strategies for using DS rodent models to enable effective and robust forward and reverse translational approaches.
Authors
- Xinxin Zuo
- Leah K. Borden (ORCID: https://orcid.org/0000-0002-8467-0444)
- Roger H. Reeves (ORCID: https://orcid.org/0000-0002-3581-0850)
- Yasuhiro Kazuki (ORCID: https://orcid.org/0000-0003-4818-4710)
- Michelle Maugham (ORCID: https://orcid.org/0000-0001-5775-5162)
- Mara Dierssen (ORCID: https://orcid.org/0000-0003-0853-6865)
- Xu‐Qiao Chen (ORCID: https://orcid.org/0000-0001-9799-7246)
- Kristy Welshhans (ORCID: https://orcid.org/0000-0001-6624-4719)
- Daniella Balduino Victorino (ORCID: https://orcid.org/0000-0002-2518-3902)
- A. G. Sathyanesan (ORCID: https://orcid.org/0000-0002-9226-7831)
- Zhuo Xing (ORCID: https://orcid.org/0000-0002-4635-6630)
- Antonella Tramutola (ORCID: https://orcid.org/0000-0002-9564-2086)
- Randall J. Roper (ORCID: https://orcid.org/0000-0002-9860-5037)
- Elizabeth Fisher (ORCID: https://orcid.org/0000-0003-2850-9936)
- Victor L. J. Tybulewicz (ORCID: https://orcid.org/0000-0003-2439-0798)
- Eitan Okun (ORCID: https://orcid.org/0000-0001-8474-1487)
- Marie‐Claude Potier (ORCID: https://orcid.org/0000-0003-2462-7150)
- Yann Hérault (ORCID: https://orcid.org/0000-0001-7049-6900)
- Andrew Folz
- Mir Abbas Raza (ORCID: https://orcid.org/0009-0002-9897-7372)
- Masaharu Hiratsuka
- William Mobley
- Y. Eugene Yu
Institutions
- University of Dayton (US)
- Centre National de la Recherche Scientifique (FR)
- Bar-Ilan University (IL)
- Johns Hopkins University (US)
- Inserm (FR)
- University of South Carolina (US)
- University of the Sunshine Coast (AU)
- Johns Hopkins Medicine (US)
- The Francis Crick Institute (GB)
- University of California San Diego (US)
- Sorbonne Université (FR)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centre for Genomic Regulation (ES)
- Cancer Genetics (United States) (US)
- National Hospital for Neurology and Neurosurgery (GB)
- Institut du Cerveau (FR)
- Chromosome Engineering Research Center (JP)
- University College London (GB)
- Tottori University (JP)
- Indiana University – Purdue University Indianapolis (US)
- Massachusetts Institute of Technology (US)
- Université de Strasbourg (FR)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- STAR Protocols
- Published
- 2026-07-25
- DOI
- https://doi.org/10.1016/j.xpro.2026.104717
- Primary Topic
- Down syndrome and intellectual disability research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Dayton
- Fundació la Marató de TV3
- Japan Agency for Medical Research and Development
- Wellcome Trust
- Francis Crick Institute
- Ministerio de Ciencia, Innovación y Universidades
- European Commission
- Agence Nationale de la Recherche
- Fondation Jérôme Lejeune
- Generalitat de Catalunya
- Université de Strasbourg
- National Institutes of Health
- Agencia Estatal de Investigación
- Eunice Kennedy Shriver National Institute of Child Health and Human Development