Expression of catecholaminergic mRNAs in the hyperactive mouse mutant coloboma.

Abstract	The SNAP-25 deficient mouse mutant coloboma (Cm/+) is an animal model for investigating the biochemical basis of locomotor hyperactivity. The spontaneous hyperactivity exhibited by coloboma is three times greater than control mice and is a direct result of the SNAP-25 deletion. SNAP-25 is a presynaptic protein that regulates exocytotic neurotransmitter release; coloboma mice express only 50% of normal protein concentrations. Previous research has determined that there is an increase in the concentration of norepinephrine but a decrease in dopamine utilization in the striatum and nucleus accumbens of coloboma mice. In situ hybridization analysis revealed that there were corresponding increases in tyrosine hydroxylase (TH) mRNA expression in noradrenergic cell bodies of the locus coeruleus of Cm/+ mice. In contrast, TH mRNA expression in substantia nigra appeared normal in the mutant mouse. alpha(2)-Adrenergic receptors are important modulators of central noradrenergic function and dopamine release. In situ hybridization data revealed that alpha(2A)-adrenergic receptor mRNA expression is upregulated in Cm/+ mice. These results suggest an underlying abnormality in noradrenergic regulation in this hyperactive mouse mutant.
Authors	M D Jones, M E Williams, E J Hess
Journal	Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 96 Issue 1-2 Pg. 114-21 (Nov 30 2001) ISSN: 0169-328X [Print] Netherlands
PMID	11731016 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Benzazepines Catecholamines Dopamine Antagonists Dopamine Plasma Membrane Transport Proteins Membrane Glycoproteins Membrane Proteins Membrane Transport Proteins Nerve Tissue Proteins RNA, Messenger Receptors, Adrenergic, alpha-2 Receptors, Dopamine Snap25 protein, mouse Synaptosomal-Associated Protein 25 Tritium Spiperone Tyrosine 3-Monooxygenase
Topics	Animals Benzazepines (metabolism, pharmacology) Catecholamines (physiology) Coloboma (genetics) Corpus Striatum (physiology) Dopamine Antagonists (metabolism, pharmacology) Dopamine Plasma Membrane Transport Proteins Female Gene Deletion Hyperkinesis (genetics) In Situ Hybridization Male Membrane Glycoproteins Membrane Proteins (genetics) Membrane Transport Proteins (genetics) Mice Mice, Inbred C3H Mice, Mutant Strains Nerve Tissue Proteins (genetics) RNA, Messenger (analysis) Radioligand Assay Receptors, Adrenergic, alpha-2 (genetics) Receptors, Dopamine (genetics) Spiperone (metabolism, pharmacology) Substantia Nigra (physiology) Synaptosomal-Associated Protein 25 Tritium Tyrosine 3-Monooxygenase (genetics)

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