Changes in GAD67 mRNA expression evidenced by in situ hybridization in the brain of R6/2 transgenic mice

• Published in: Journal of neurochemistry Vol. 86; no. 6; pp. 1369 - 1378
• Main Authors: Gourfinkel‐An, I., Parain, K., Hartmann, A., Mangiarini, L., Brice, A., Bates, G., Hirsch, E. C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2003; Blackwell
• Subjects: Animals; Biological and medical sciences; Brain - metabolism; Brain - parasitology; cortex; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Disease Progression; GABA; Glutamate Decarboxylase - genetics; Humans; Huntington; Huntington Disease - metabolism; Huntington Disease - pathology; In Situ Hybridization; Isoenzymes - genetics; Medical sciences; Mice; Mice, Transgenic; Neurology; polyglutamine; RNA, Messenger - metabolism; striatum; Trinucleotide Repeat Expansion; Cerebral cortex; Lyases; Huntington; striatum; Carboxy-lyases; Degenerative disease; Degeneration; cortex; Nervous system diseases; Enzyme; Rodentia; Huntington disease; Corpus striatum; Glutamate decarboxylase; Basal ganglion; Gene expression; polyglutamine; Cerebral disorder; Genetic disease; Carbon-carbon lyases; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; GABA; Extrapyramidal syndrome
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.01916.x

Huntington's disease is an autosomal dominant disorder with degeneration of medium size striatal neurones. As the disease evolves, other neuronal populations are also progressively affected. A transgenic mouse model of the disease (R6/2) that expresses exon 1 of the human Huntington gene with approximately 150 CAG repeats has been developed, but GABA concentrations are reported to be normal in the striatum of these animals. In the present study, we analysed the status of GABAergic systems by means of glutamic acid decarboxylase (GAD)67 mRNA in situ hybridization in the brain of R6/2 transgenic mice and wild‐type littermates. We show that GAD67 expression is normal in the striatum, cerebellum and septum but decreased in the frontal cortex, parietal cortex, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata of R6/2 mice. These data, which may, in part, account for the behavioural changes seen in these animals, indicate that at 12.5 weeks of age the pathological features seen in the mice differ from those seen in humans with Huntington's disease.