What Can Genetic Models Tell Us About Attention-Deficit Hyperactivity Disorder (ADHD)?

Fulvio Magara-Acallosal Mice & ADHD

Dr. Magara I am struck by the variability you see in terms of spontaneous activity as well as other behavioral parameters (avoidance for example) in the acallosal I/ln mice. Whatever the mechanism this is, it is very much the kind of heterogeneity we see in the locomotor activity of coloboma mutants - with some mice attaining 10 fold the activity as wild type and yet others being quite inactive. Interestingly, both treatment with a relatively low dose of amphethamine or gene rescue with a SNAP-25 transgene not only decreases the spontaneous activity but also greatly reduces the variability in activity in these mutant mice. Both models, despite their clearly distinct origins (and possibly mechanisms) seem to to fit in with the idea of dysregulation of control quite nicely, perhaps that mediated through executive functions performed by prefrontal cortex, as proposed by Barkley. Have you tested the activity of these mice after psychostimulant drugs?
Also perhaps as an aside, I was interested to hear if you have any information regarding 129 strain mice. This strain has been reported to be acallosal to a various degree. Should lack of interhemispheric connectivity result in dysregulation (for which I believe you have made a strong case), this may have considerable implications for the generation of homologous recombinant "knockout" mice which are, as you likely know, made with 129 ES cells and are generally developed on either a 129 or mixed 129/C57Bl/6 background.
-Michael Wilson

Fri Dec 11