DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects.
Among the various phenotypes seen in Down syndrome (DS), mental retardation is the most common and most debilitating condition suffered by individuals with DS. The DYRK1A gene on human chromosome 21q22.2 encodes a subfamily of protein kinases that displays dual substrate specificities and is known to play a critical role in neurodevelopment. To study DS mental retardation, we have generated transgenic mice that contain only one copy of the complete human DYRK1A gene in a bacterial artificial chromosome. The transgenic mice showed significant impairment in hippocampal-dependent memory tasks in a Morris water maze. Interestingly, we observed shifts in both long-term potentiation and long-term depression, which suggests a role for DYRK1A in bidirectional synaptic plasticity. These mice represent the most clinically relevant DYRK1A mouse model to date and provide us a valuable tool for the in vivo study of mechanisms that underlie the learning and memory deficit in DS.
Ahn
Kyoung-Jin
KJ
Graduate Program in Neuroscience and Institute for Brain Science and Technology (IBST), Inje University, Daejeon 305-804, Republic of Korea.
Jeong
Hey Kyeong
HK
Choi
Han-Saem
HS
Ryoo
Soo-Ryoon
SR
Kim
Yeon Ju
YJ
Goo
Jun-Seo
JS
Choi
Se-Young
SY
Han
Jung-Soo
JS
Ha
Ilho
I
Song
Woo-Joo
WJ
D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007859:Learning Disabilities / Q000235:genetics*; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases
D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases