Phenotypes associated with this allele

• Allele Symbol: Bace1^tm1Pcw
• Allele Name: targeted mutation 1, Philip C Wong
• Allele ID: MGI:2389228
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bace1^tm1Pcw/Bace1^tm1Pcw	involves: 129S1/Sv * 129X1/SvJ	MGI:3720951
hm2	Bace1^tm1Pcw/Bace1^tm1Pcw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3720943
cx3	Bace1^tm1Pcw/Bace1^tm1Pcw Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J	MGI:3720944
cx4	Bace1^tm1Pcw/Bace1^+ Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J	MGI:3720945
cx5	Bace1^tm1Pcw/Bace1^+ Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-CDK5R1/GFP)337Lht/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5634918

Genotype
MGI:3720951

hm1

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

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

behavior/neurological

decreased grip strength ( J:116162 )

• mice show reduced grip strength (1.13) relative to wild-type controls (1.26)

decreased thermal nociceptive threshold ( J:116162 )

• mutants retract paws from thermal stimulus more rapidly than wild-type controls, indicating greater pain sensitivity

nervous system

abnormal myelin sheath morphology ( J:116162 )

• in 2-month old mice, myelin sheaths are significantly thinner in optic nerves compared to wild-type controls

• more axons in sciatic nerve of mutants appear smaller in diameter than in wild-type

abnormal myelination ( J:116162 )

• hypomyelination is observed in hippocampus and cerebral cortex at P15 and P30, but axonal development is normal

• sciatic nerve is hypomyelinated in mutants

Genotype
MGI:3720943

hm2

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

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 )

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

♂ • latencies of startle reaction are longer in mutants

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

Genotype
MGI:3720944

cx3

• Allelic Composition: Bace1^tm1Pcw/Bace1^tm1Pcw; Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:123534 )

N • mice perform as well as control mice in platform and probe trials in Morris water maze tasks

decreased anxiety-related response ( J:123534 )

• in open field test, mice are similar to Bace1^tm1Pcw homozygotes, and spend more time in open area at center of field than at periphery

abnormal locomotor activation ( J:123534 )

• swim speed is lower than other genotypes and nontransgenic mice in hidden and visible platform trials

nervous system

nervous system phenotype ( J:123534 )

N • in 12- or 20-month old mice, no amyloid beta (Abeta) aggregation is detected in brains; no amyloid deposits are found

Genotype
MGI:3720945

cx4

• Allelic Composition: Bace1^tm1Pcw/Bace1⁺; Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J

behavior/neurological

abnormal spatial learning ( J:123534 )

abnormal spatial reference memory ( J:123534 )

• mice are significantly impaired in Morris water maze tasks

nervous system

amyloid beta deposits ( J:123534 )

• high level of amyloid beta aggregates are found in brain at 12 months of age

homeostasis/metabolism

amyloidosis ( J:123534 )

• in 12-month old brains, there is a 27% reduction in amyloid beta aggregates compared to transgenic mice that are wild-type for Bace1; there are no significant differences at 20 months

• in 12-month old brains, there is 37% reduction in percentage of brain volume occupied by amyloid beta deposits, but no difference at 20 months

amyloid beta deposits ( J:123534 )

• high level of amyloid beta aggregates are found in brain at 12 months of age

Genotype
MGI:5634918

cx5

• Allelic Composition: Bace1^tm1Pcw/Bace1⁺; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-CDK5R1/GFP)337Lht/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

nervous system phenotype ( J:177847 )

N • mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit decreased amyloid beta in the hippocampus

N • mice exhibit normal synaptic plasticity and long term potentiation (LTP) is fully restored following a 6-week induction

N • mice exhibit normal density of synaptophysin puncta in the stratum radiatum of the hippocampus, indicating restoration of synapse density, following a 6-week induction

decreased brain weight ( J:177847 )

• brain weight is reduced in 6-week induced mice

hippocampal neuron degeneration ( J:177847 )

• reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice

astrocytosis ( J:177847 )

• reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice

behavior/neurological

behavior/neurological phenotype ( J:177847 )

N • 6-week induced mice show improved associate learning in contextual fear conditioning and are indistinguishable from controls