Expression of catecholaminergic mRNAs in the hyperactive mouse mutant coloboma.
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.
Jones
M D
MD
Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
Williams
M E
ME
Hess
E J
EJ
D000818:Animals; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology*; D003103:Coloboma / Q000235:genetics*; D003342:Corpus Striatum / Q000502:physiology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D017353:Gene Deletion; D006948:Hyperkinesis / Q000235:genetics*; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics; D013134:Spiperone / Q000378:metabolism / Q000494:pharmacology; D013378:Substantia Nigra / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25; D014316:Tritium; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D001552:Benzazepines; D002395:Catecholamines; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D011954:Receptors, Dopamine; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D014316:Tritium; D013134:Spiperone; D014446:Tyrosine 3-Monooxygenase