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Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior
Citation
Gantios, I and Fang, K and Jiang, L and Babovic, D and Lawrence, AL and Ferreri, V and Teper, Y and Jupp, B and Ziebell, JM and Morganti-Kossmann, CM and O'Brien, TJ and Nally, R and Schutz, G and Waddington, J and Egan, GF and Drago, J, Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior, National Academy of Sciences of The United States of America. Proceedings, 104, (10) pp. 4182-4187. ISSN 0027-8424 (2007) [Refereed Article]
Copyright Statement
Copyright 2007 The National Academy of Sciences of the USA
Official URL: http://www.pnas.org/content/104/10/4182.abstract
DOI: 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 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 tongueprotrusion
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | striatum; cre; Huntington's Disease |
| Research Division: | Biological Sciences |
| Research Group: | Genetics |
| Research Field: | Neurogenetics |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Ziebell, JM (Dr Jenna Ziebell) |
| ID Code: | 101704 |
| Year Published: | 2007 |
| Web of Science® Times Cited: | 56 |
| Deposited By: | Wicking Dementia Research and Education Centre |
| Deposited On: | 2015-07-02 |
| Last Modified: | 2022-09-02 |
| Downloads: | 0 |
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