Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior

Ilse Gantois; Ke Fang; Luning Jiang; Daniela Babovic; Andrew J Lawrence; Vincenzo Ferreri; Yaroslav Teper; Bianca Jupp; Jenna Ziebell; Cristina M Morganti-Kossmann; Terence J O'Brien; Rachel Nally; Guenter Schuetz; John Waddington; Gary F Egan; John Drago

Journal article

Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior

Ilse Gantois, Ke Fang, Luning Jiang, Daniela Babovic, Andrew J Lawrence, Vincenzo Ferreri, Yaroslav Teper, Bianca Jupp, Jenna Ziebell, Cristina M Morganti-Kossmann, Terence J O'Brien, Rachel Nally, Guenter Schuetz, John Waddington, Gary F Egan, John Drago

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2007

DOI: 10.1073/pnas.0611625104

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 ..

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