Title: Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior
Authors: Gantois, Ilse ×
Fang, Ke
Jiang, Luning
Babovic, Daniela
Lawrence, Andrew J
Ferreri, Vincenzo
Teper, Yaroslav
Jupp, Bianca
Ziebell, Jenna
Morganti-Kossmann, Cristina M
O'Brien, Terence J
Nally, Rachel
Schuetz, Günter
Waddington, John
Egan, Gary F
Drago, John #
Issue Date: Mar-2007
Publisher: Natl acad sciences
Series Title: Proceedings of the national academy of sciences of the united states of america vol:104 issue:10 pages:4182-4187
Abstract: Huntington's disease is characterized by death of striatal projection neurons. We used a Cre/Lox transgenic approach to generate an animal model in which D1 dopamine receptor (Drd1a)+ cells are progressively ablated in the postnatal brain. Striatal Drd1a, substance P, and dynorphin expression is progressively lost, whereas D2 dopamine receptor (Drd2) and enkephalin expression is up-regulated. Magnetic resonance spectroscopic analysis demonstrated early elevation of the striatal choline/creatine ratio, a finding associated with extensive reactive striatal astrogliosis. Sequential MRI demonstrated a progressive reduction in striatal volume and secondary ventricular enlargement confirmed to be due to loss of striatal cells. Mutant mice had normal gait and rotarod performance but displayed hindlimb dystonia, locomotor hyperactivity, and handling-induced electrographically verified spontaneous seizures. Ethological assessment identified an increase in rearing and impairments in the oral behaviors of sifting and chewing. In line with the limbic seizure profile, cell loss, astrogliosis, microgliosis, and down-regulated dynorphin expression were seen in the hippocampal dentate gyrus. This study specifically implicates Drd1a+ cell loss with tail suspension hindlimb dystonia, hyperactivity, and abnormal oral function. The latter may relate to the speech and swallowing disturbances and the classic sign of tongue-protrusion motor impersistence observed in Huntington's disease. In addition, the findings of this study support the notion that Drd1a and Drd2 are segregated on striatal projection neurons.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
× corresponding author
# (joint) last author

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