Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression.
OBJECTIVES. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1).


METHODS
DN-DISC1 mice underwent behavioural tests to evaluate object recognition, social preference and social novelty seeking. ELISA was conducted on brain tissue to evaluate BDNF levels. Western blot was employed to measure BDNF receptor (TrkB) and cannabinoid receptor CB1.


RESULTS
The mutant DISC1 mice displayed deficits in preference to social novelty while both social preference and object recognition were intact. Biochemical analysis of prefrontal cortex and hippocampus revealed a modest reduction in cortical TrkB protein levels of male mice while no differences in BDNF levels were observed. We found sex dependent differences in the expression of cannabinoid-1 receptors.


CONCLUSIONS
We describe novel behavioural and biochemical abnormalities in the DN-DISC1 mouse model of schizophrenia. The data shows for the first time a possible link between DISC1 mutation and the cannabinoid system.
Biological Psychiatry Lab, Felsenstein Medical Research Center, Beilinson Campus, Sackler Faculty of Medicine, Tel Aviv University , Israel.
Ayelet
A
Kaminitz
Ran
R
Barzilay
Hadar
H
Segal
Michal
M
Taler
Daniel
D
Offen
Irit
I
Gil-Ad
Raphael
R
Mechoulam
Abraham
A
Weizman
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004195:Disease Models, Animal; D005799:Genes, Dominant / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D020813:Receptor, trkB / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012919:Social Behavior
D019208:Brain-Derived Neurotrophic Factor; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D043884:Receptor, Cannabinoid, CB1; D020813:Receptor, trkB