Phenotypes Associated with This Genotype

Genotype
MGI:3707976

• Allelic Composition: Disc1^Rgsc1390/Disc1⁺
• Genetic Background: B6.Cg-Disc1^Rgsc1390

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

behavior/neurological phenotype ( J:120634 )

N • the time spent on the open arms of the elevated plus maze by heterozygous mutant and wild-type mice is similar, indicating they experience similar anxiety levels

N • in tests of sociability and social novelty, both heterozygous and homozygous mutant, like wild-type, mice spend more time in a chamber with an unfamiliar mouse than in an unoccupied chamber and more time in a chamber with a new unfamiliar mouse than with one to which they previously have been introduced

abnormal latent inhibition of conditioning behavior ( J:120634 )

• both homozygous and heterozygous mutant mice exhibit disruption in latent inhibition (LI) of fear conditioning by pre-training exposure to the conditioned neutral stimulus (CS; sound) without the noxious unconditioned stimulus (US; shock)

• the antipsychotic clozapine does not restore LI in mice heterozygous for this mutation

• both homozygous and heterozygous mutant mice that are not not pre-exposed to the unpaired neutral stimulus acquire a strong US/CS association

decreased startle reflex ( J:120634 )

• in the absence of a prepulse, the amplitude of the acoustic startle response in mice heterozygous for this mutation is significantly lower (p<0.001) than in wild-type mice

• neither homozygous nor heterozygous mutants showed improvement in acoustic startle response when treated with haloperidol, clozapine, bupropion or rolipram

• the diminished startle response of mice with this mutation is not due to impaired hearing, as the auditory brainstem response (ABR) threshold of homozygous mutant mice at 16 kHz (40 +/- 2.6) is similar to that of wild type mice (46 +/- 5.1)

nervous system

decreased brain size ( J:120634 )

• magnetic resonance imaging (MRI) reveals that the brain volumes of mice homozygous or heterozygous for this mutation are 13% lower than those of wild-type mice

small thalamus ( J:120634 )

• MRI reveals contraction of the thalamus in heterozygous and homozygous mutant mice

abnormal entorhinal cortex morphology ( J:120634 )

• MRI reveals contraction of the entorhinal cortex in heterozygous and homozygous mutant mice

thin cerebral cortex ( J:120634 )

• MRI reveals contraction around the cerebral cortex, without alteration of white-matter tracts, in heterozygous and homozygous mutant mice

small cerebellum ( J:120634 )

• MRI reveals contraction of the cerebella of heterozygous and homozygous mutant mice

abnormal prepulse inhibition ( J:120634 )

• mice heterozygous for this mutation exhibit much lower prepulse inhibition (PPI; p<0.001), i.e., less reduction of the startle response following a prepulse, than do wild-type mice

• the antipsychotic haloperidol, a dopamine D2 receptor antagonist, partially alleviates the aberrant PPI of heterozygous mutant mice

• the antipsychotic clozapine, a combined dopamine D2 and serotonin receptor antagonist that also increases PPI in wild-type mice, partially alleviates the aberrant PPI in heterozygous mutant mice

• the antidepressant bupropion, a combined dopamine and norepinephrine reuptake inhibitor, has no effect on the abnormal PPI of heterozygous mutant mice

• the phosphodiesterase 4 (PDE4) inhibitor rolipram abolishes the PPI deficit of mice with this mutation

• the defective prepulse inhibition of mice with this mutation is not due to impaired hearing, as the auditory brainstem response (ABR) threshold of homozygous mutant mice at 16 kHz (40 +/- 2.6) is similar to that of wild-type mice (46 +/- 5.1)