Phenotypes associated with this allele

• Allele Symbol: App^tm1Cwe
• Allele Name: targeted mutation 1, Charles Weissmann
• Allele ID: MGI:2154522
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	App^tm1Cwe/App^tm1Cwe	129S-App^tm1Cwe	MGI:2177025
hm2	App^tm1Cwe/App^tm1Cwe	B6.129S2-App^tm1Cwe	MGI:3590205
hm3	App^tm1Cwe/App^tm1Cwe	involves: 129S2/SvPas	MGI:3718912
hm4	App^tm1Cwe/App^tm1Cwe	involves: 129S2/SvPas * C57BL/6	MGI:2177008

Genotype
MGI:2177025

hm1

• Allelic Composition: App^tm1Cwe/App^tm1Cwe
• Genetic Background: 129S-App^tm1Cwe

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

nervous system

decreased brain weight ( J:54584 )

• brain weight is reduced 10% relative to controls

abnormal brain commissure morphology ( J:54584 )

absent corpus callosum ( J:54584 )

• Background Sensitivity: greatly increased frequency of absent corpus callosum over controls in 129-derived genetic backgrounds

decreased hippocampal commissure size ( J:54584 )

• Background Sensitivity: greatly reduced ventral hippocampal commissure; 71% reduced compared to controls

decreased anterior commissure size ( J:54584 )

• reduced size of anterior commissure, independent of genetic background

Genotype
MGI:3590205

hm2

• Allelic Composition: App^tm1Cwe/App^tm1Cwe
• Genetic Background: B6.129S2-App^tm1Cwe

nervous system

decreased brain weight ( J:54584 )

• brain weight is reduced 10% relative to controls

abnormal brain commissure morphology ( J:54584 )

decreased corpus callosum size ( J:54584 )

• Background Sensitivity: 4-11% smaller than controls; absence of corpus callosum is not statistically significant in mutant lines with greater than 50% C57BL/6 genetic background contrbution when compared to controls

decreased hippocampal commissure size ( J:54584 )

• Background Sensitivity: slightly reduced ventral hippocampal commissure; 13% reduced compared to controls

decreased anterior commissure size ( J:54584 )

• reduced size of anterior commissure, independent of genetic background

Genotype
MGI:3718912

hm3

• Allelic Composition: App^tm1Cwe/App^tm1Cwe
• Genetic Background: involves: 129S2/SvPas

behavior/neurological

abnormal spatial learning ( J:123316 )

• take about twice as long to find the platform and swim greater distances in a water maze

abnormal emotion/affect behavior ( J:123316 )

decreased exploration in new environment ( J:123316 )

• decreased exploratory behavior under aversive conditions

increased thigmotaxis ( J:123316 )

• increased wall-hugging in a water maze

abnormal motor capabilities/coordination/movement ( J:123316 )

impaired swimming ( J:123316 )

• swim speed is decreased by 19% compared to controls

decreased grip strength ( J:123316 )

• grip strength deficit of 23% compared to controls

abnormal locomotor activation ( J:123316 )

• significantly increased activity levels at the beginning of the dark period and decreased activity levels at the end of the dark period compared to controls

abnormal circadian behavior ( J:123316 )

• abnormal circadian distribution of activity

nervous system

decreased brain weight ( J:123316 )

• brain wet weight is reduced by about 11% at 10 - 12 months of age

reduced long-term potentiation ( J:123316 )

• deficit in long term potentiation in mice at 9 to 12 months of age

growth/size/body

decreased body weight ( J:123316 )

• reduced by about 15% and 19% compared to wild-type in females and males, respectively at 2.4 months of age

Genotype
MGI:2177008

hm4

• Allelic Composition: App^tm1Cwe/App^tm1Cwe
• Genetic Background: involves: 129S2/SvPas * C57BL/6

growth/size/body

decreased body weight ( J:21937 )

• on average, mutant mice weigh 10% less than controls

nervous system

nervous system phenotype ( J:54584 )

N • Background Sensitivity: absence of corpus callosum is not statistically significant in mutant lines with greater than 50% C57BL/6 genetic background contribution when compared to controls

decreased brain weight ( J:54584 )

• brain weight is reduced 10% relative to controls

abnormal brain commissure morphology ( J:54584 )

absent corpus callosum ( J:21937 )

• corpus callosum absent in 7 of 9 homozygous mutant pups, but only 1 of 8 heterozygotes and 1 of 8 wild-type controls, suggesting that this mutation contributes to an underlying predisposition for this trait in 129 substrain mice

decreased hippocampal commissure size ( J:54584 )

• Background Sensitivity: slightly reduced ventral hippocampal commissure; 16% reduced compared to controls

decreased anterior commissure size ( J:54584 )

• reduced size of anterior commissure, independent of genetic background

behavior/neurological

abnormal learning/memory/conditioning ( J:21937 )

abnormal cued conditioning behavior ( J:21937 )

• in a two-chamber box test, mutant mice did not learn to avoid a shock by running from one chamber to another after a warning light conditioning stimulus

decreased exploration in new environment ( J:21937 )

• mice show decreased exploratory stops during and after habituation in a new environment

• total path length covered by the mutant mice is 70% of that of controls

abnormal spatial reference memory ( J:21937 )

• mutant mice show a reduced ability to use visual cues after habituation to find a platform in the Morris water maze test

• significant behavioral differences to controls are reflected in total swimming time, percentage of time in the target quadrant and orientation towards the sunken platform

• the learning defect is not due to visual defects

abnormal fear/anxiety-related behavior ( J:21937 )

increased thigmotaxis ( J:21937 )

• mice exhibit increased thigmotaxis (stopping along walls) and fewer excursions into the open field after habituation to a new environment