Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes

Lana-Elola, Eva, Cater, Heather, Watson-Scales, Sheona, Greenaway, Simon, Müller-Winkler, Jennifer, Gibbins, Dorota, Nemes, Mihaela, Slender, Amy, Hough, Tertius, Keskivali-Bond, Piia, Scudamore, Cheryl L., Herbert, Eleanor, Banks, Gareth T., Mobbs, Helene, Canonica, Tara, Tosh, Justin, Noy, Suzanna, Llorian, Miriam, Nolan, Patrick M., Griffin, Julian L., Good, Mark ORCID: https://orcid.org/0000-0002-1824-1203, Simon, Michelle, Mallon, Ann-Marie, Wells, Sara, Fisher, Elizabeth M. C. and Tybulewicz, Victor L. J. 2021. Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes. Disease Models and Mechanisms 14 (10) , 049157. 10.1242/dmm.049157

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Abstract

Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, these dosage-sensitive causative genes remain unknown. Animal models enable identification of genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. In order to establish whether this model recapitulates DS phenotypes, we comprehensively phenotyped Dp1Tyb mice using 28 tests of different physiological systems and found that 468 out of 1800 parameters were significantly altered. We show that Dp1Tyb mice have wide-ranging DS-like phenotypes, including aberrant erythropoiesis and megakaryopoiesis, reduced bone density, craniofacial changes, altered cardiac function, a pre-diabetic state, and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for investigating complex DS phenotype-genotype relationships for this common disorder.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0)
Publisher:	The Company of Biologists
ISSN:	1754-8403
Date of First Compliant Deposit:	8 November 2021
Date of Acceptance:	26 August 2021
Last Modified:	06 May 2023 10:56
URI:	https://orca.cardiff.ac.uk/id/eprint/145356

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