TY - JOUR
T1 - Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes
AU - Lana-Elola, Eva
AU - Cater, Heather
AU - Watson-Scales, Sheona
AU - Greenaway, Simon
AU - Müller-Winkler, Jennifer
AU - Gibbins, Dorota
AU - Nemes, Mihaela
AU - Slender, Amy
AU - Hough, Tertius
AU - Keskivali-Bond, Piia
AU - Scudamore, Cheryl L.
AU - Herbert, Eleanor
AU - Banks, Gareth T.
AU - Mobbs, Helene
AU - Canonica, Tara
AU - Tosh, Justin
AU - Noy, Suzanna
AU - Llorian, Miriam
AU - Nolan, Patrick M.
AU - Griffin, Julian L.
AU - Good, Mark
AU - Simon, Michelle
AU - Mallon, Ann Marie
AU - Wells, Sara
AU - Fisher, Elizabeth M.C.
AU - Tybulewicz, Victor L.J.
PY - 2021/10
Y1 - 2021/10
N2 - 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 dosagesensitive 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 prediabetic 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.
AB - 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 dosagesensitive 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 prediabetic 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.
KW - Craniofacial development
KW - Diabetes
KW - Down syndrome
KW - Haematopoiesis
KW - Hearing
KW - Memory
KW - Mouse model
KW - Sleep
UR - http://www.scopus.com/inward/record.url?scp=85118269264&partnerID=8YFLogxK
U2 - 10.1242/dmm.049157
DO - 10.1242/dmm.049157
M3 - Article
C2 - 34477842
AN - SCOPUS:85118269264
VL - 14
JO - DMM Disease Models and Mechanisms
JF - DMM Disease Models and Mechanisms
SN - 1754-8403
IS - 10
M1 - dmm049157
ER -