Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypesMore about Open Access at the Crick
Authors listEva Lana-Elola Heather Cater Sheona Watson-Scales Simon Greenaway Jennifer Mueller-Winkler Dorota Gibbins Mihaela Nemes Amy Slender Tertius Hough Piia Keskivali-Bond Cheryl L Scudamore Eleanor Herbert Gareth T Banks Helene Mobbs Tara Canonica Justin Tosh Suzanna Noy Miriam Llorian Patrick M Nolan Julian L Griffin Mark Good Michelle Simon Ann-Marie Mallon Sara Wells Elizabeth MC Fisher Victor Tybulewicz
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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 if 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.
Journal Disease Models and Mechanisms
Issue number 10