Coloboma mouse mutant as an animal model of hyperkinesis and attention deficit hyperactivity disorder

Neurosci Biobehav Rev. 2000 Jan;24(1):51-7. doi: 10.1016/s0149-7634(99)00064-0.


Hyperkinesis and developmental behavioral deficiencies are cardinal signs of attention-deficit hyperactivity disorder. In mice, the mutation coloboma (Cm) corresponds to a contiguous gene defect that results in phenotypic abnormalities including spontaneous hyperactivity, head-bobbing, and ocular dysmorphology. In addition, coloboma mutant mice exhibit delays in achieving complex neonatal motor abilities and deficits in hippocampal physiology, which may contribute to learning deficiencies. The hyperkinesis is ameliorated by low doses of the psychostimulant D-amphetamine and can be rescued genetically by a transgene encoding SNAP-25, located within the Cm deletion. Together with syntaxin and synaptobrevin/VAMP, SNAP-25 constitutes a core protein complex integral to synaptic vesicle fusion and neurotransmitter release. Despite the ubiquitous role of SNAP-25 in synaptic transmission, and uniformly decreased expression in the mutants, coloboma mice show marked deficits in Ca2+-dependent dopamine release selectively in dorsal but not ventral striatum. This suggests that haploinsufficiency of SNAP-25 reveals a specific vulnerability of the nigrostriatal pathway which regulates motor activity and may provide a model for impaired striatal input into executive functions encoded by the prefrontal cortex associated with ADHD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Coloboma / genetics*
  • Coloboma / metabolism
  • Coloboma / psychology
  • Hyperkinesis / genetics*
  • Hyperkinesis / metabolism
  • Hyperkinesis / psychology
  • Mice
  • Mice, Neurologic Mutants / genetics
  • Mice, Neurologic Mutants / psychology*