Phenotypes Associated with This Genotype

Genotype
MGI:3720943

• Allelic Composition: Bace1^tm1Pcw/Bace1^tm1Pcw
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

behavior/neurological

enhanced behavioral response to xenobiotic ( J:133643 )

♂ • mice treated with the psychostimulant dizocilpine show higher levels of drug-stimulated motor activation than wild-type mice

impaired passive avoidance behavior ( J:133643 )

♂ • mice are impaired in the inhibitory avoidance memory task

abnormal dishabituation ( J:133643 )

♂ • mice show decreased social investigation time for dishabituation phases of the task

♂ • an inability of mutants to dissociate between the new and familiar mouse is accentuated when the genetic background of the stimulus mice (Swiss-Webster) differs from that of mutants

abnormal spatial learning ( J:123534 )

abnormal spatial reference memory ( J:123534 )

• in Morris water maze, 3-month old mice show normal learning and memory for location of hidden platform, but at 16 months, mutant animals display significantly impaired spatial reference memory during probe trials compared to normal or heterozygous littermates, while performance in hidden platform trials is not significantly different

abnormal spatial working memory ( J:123534 , J:133643 )

• in spatial working memory tasks using the radial arm water maze, mice are significantly impaired compared to littermates; deficit is observed in Y-maze task, with mutant animals showing deficits in arm alternation (J:123534)

♂ • mice are impaired in the in the radial water maze task, specifically in errors in working but not long-term memory (J:133643)

♂ • treatment with clozapine has no effect on working memory (J:133643)

decreased anxiety-related response ( J:123534 )

• in an open-field task, mice display low anxiety-type behavior like greater distance traveled and more frequent and active visits to open center of field compared to control heterozygotes and wild-type mice

abnormal response to novel object ( J:133643 )

♂ • mutants show higher novelty-induced activity in the open-field, plus maze, corner test, and Y maze

♂ • treatment with clozapine attenuates novelty-induced hyperactivity

abnormal startle reflex ( J:133643 )

♂ • latencies of startle reaction are longer in mutants

♂ • however, there is no correlation between latency of startle reaction to deficit in prepulse inhibition

abnormal locomotor activation ( J:123534 )

• swimming speed is lower than controls in Morris water maze

nervous system

abnormal dendritic spine morphology ( J:133643 )

♂ • decrease in the spine densities of CA1 pyramidal neurons

♂ • mice show a reduction in the number of spines per dendrite

♂ • dendrites show a smaller proportion of mushroom-shaped spines, particularly in neurons with medium to high spine loads

♂ • however, dendritic arborization is normal

decreased prepulse inhibition ( J:133643 )

♂ • mice show deficits in prepulse inhibition of acoustic startle response

♂ • however, startle amplitudes are not different from wild-type mice

♂ • treatment with the antipsychotic clozapine ameliorates prepulse inhibition defects

abnormal long-term depression ( J:123534 )

• after LTD saturation, mice display a larger de-depression than controls

enhanced paired-pulse facilitation ( J:123534 )

• the PPF ratio is significantly increased at short interstimulus intervals (ISIs) relative to controls, but not at long ISIs

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:133643