Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation.
Although hyperkinesis is expressed in several neurological disorders, the biological basis of this phenotype is unknown. The mouse mutant coloboma (Cml+) exhibits profound spontaneous locomotor hyperactivity resulting from a deletion mutation. This deletion encompasses several genes including Snap, which encodes SNAP-25, a nerve terminal protein involved in neurotransmitter release. Administration of amphetamine, a drug that acts presynaptically, markedly reduced the locomotor activity in coloboma mice but increased the activity of control mice implicating presynaptic function in the behavioral abnormality. In contrast, the psychostimulant methylphenidate increased locomotor activity in both coloboma and control mice. When a transgene encoding SNAP-25 was bred into the coloboma strain to complement the Snap deletion, the hyperactivity expressed by these mice was rescued, returning these corrected mice to normal levels of locomotor activity. These results demonstrate that the hyperactivity exhibited by these mice is the result of abnormalities in presynaptic function specifically attributable to deficits in SNAP-25 expression.
Hess
E J
EJ
Department of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, Hershey Medical Center, 17033, USA.
Collins
K A
KA
Wilson
M C
MC
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003103:Coloboma / Q000235:genetics / Q000662:veterinary*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation; D006948:Hyperkinesis / Q000503:physiopathology* / Q000523:psychology; D017403:In Situ Hybridization; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D012376:Rodent Diseases / Q000503:physiopathology* / Q000523:psychology; D050825:Synaptosomal-Associated Protein 25; D019076:Transgenes
D018491:Dopamine Agonists; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D000661:Amphetamine