All Phenotypes Psen1<tm1Mpm> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Psen1^tm1Mpm
targeted mutation 1, Mark P Mattson
MGI:1930937

Summary

12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Psen1^tm1Mpm/Psen1^tm1Mpm	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2174994
ht2	Psen1^tm1Mpm/Psen1^tm1Shn	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:5292245
ht3	Psen1^tm1Mpm/Psen1^tm1Pcw	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	MGI:3702925
cx4	App^tm1Ck/App^tm1Ck Psen1^tm1Mpm/Psen1^tm1Mpm Tg(MAPT)8cPdav/0	B6.Cg-Tg(MAPT)8cPdav Psen1^tm1Mpm App^tm1Ck	MGI:5581681
cx5	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?	B6.Cg-Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa	MGI:5003275
cx6	App^tm1Ck/App^tm1Ck Psen1^tm1Mpm/Psen1^tm1Mpm	involves: 129 * 129S1/Sv * 129X1/SvJ	MGI:4847595
cx7	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/0 Tg(Thy1-YFP)HJrs/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4834196
cx8	Cx3cr1^tm1Litt/Cx3cr1⁺ Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/0 Tg(Thy1-YFP)HJrs/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4834197
cx9	App^tm3.1Zhe/App^tm3.1Zhe Psen1^tm1Mpm/Psen1^tm1Mpm	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:4847594
cx10	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3720782
cx11	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3720789
cx12	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSWE)2576Kha/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5292247

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Mpm
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)

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

nervous system

increased susceptibility to neuronal excitotoxicity ( J:51950 )

• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type

• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

neurodegeneration ( J:51950 )

• homozygotes are hypersensitive to seizure-induced synaptic degeneration and necrotic neuronal death in the hippocampus

behavior/neurological

behavior/neurological phenotype ( J:91277 , J:99604 )

N	• homozygotes do not exhibit a deficit in contextual fear learning at 3 months of age (J:91277) • homozygous mice do not differ in performance in Morris water maze or in contextual fear conditioning (J:99604)

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:51950 )

• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type

• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

cellular

increased susceptibility to neuronal excitotoxicity ( J:51950 )

• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type

• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease	DOID:10652		J:51950
Alzheimer's disease 3	DOID:0110042	OMIM:607822	J:51950

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Shn
Genetic Background	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Psen1^tm1Shn mutation (2 available); any Psen1 mutation (48 available)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:175901 )

• at E15 to E18

limbs/digits/tail

abnormal limb development ( J:175901 )

• limb ateliosis

short tail ( J:175901 )

• stubby

cardiovascular system

hemorrhage ( J:175901 )

• in the central nervous system

growth/size/body

decreased fetal size ( J:175901 )

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Pcw
Genetic Background	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Psen1^tm1Pcw mutation (0 available); any Psen1 mutation (48 available)

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

behavior/neurological

abnormal contextual conditioning behavior ( J:91277 )

• exhibit impaired hippocampus-dependent contextual fear learning at 3 months of age, showing reduced freezing behavior

• however, show normal cued fear learning, anxiety, motor coordination and shock threshold

nervous system

abnormal neuron differentiation ( J:91277 )

• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

cellular

abnormal neuron differentiation ( J:91277 )

• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease	DOID:10652		J:91277
Alzheimer's disease 3	DOID:0110042	OMIM:607822	J:91277

Allelic Composition	App^tm1Ck/App^tm1Ck Psen1^tm1Mpm/Psen1^tm1Mpm Tg(MAPT)8cPdav/0
Genetic Background	B6.Cg-Tg(MAPT)8cPdav Psen1^tm1Mpm App^tm1Ck

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
App^tm1Ck mutation (0 available); any App mutation (105 available)
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Tg(MAPT)8cPdav mutation (2 available)

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

behavior/neurological

enhanced contextual conditioning behavior ( J:209782 )

• mice show increased contextual freezing frequency at 4 and 12 months of age

• however, cued freezing frequency is unaffected and mice do not exhibit spatial memory deficits in the Morris water maze

increased anxiety-related response ( J:209782 )

• in the elevated plus maze, 4 month old mice spend less time on the open arm, indicating increased anxiety

• however, mice show normal nociception in the hot plate assay

increased fear-related response ( J:209782 )

• mice show slightly higher pre-shock freezing frequency and increased contextual freezing frequency at 4 and 12 months of age, indicating exaggerated fear response

decreased locomotor activity ( J:209782 )

• in the open field, the total travel distance is reduced at 12, but not 4, months of age, indicating age-dependent reduced activity

homeostasis/metabolism

amyloid beta deposits ( J:209782 )

• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age

nervous system

amyloid beta deposits ( J:209782 )

• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age

tau protein deposits ( J:209782 )

• increase in phosphorylated tau in the cortex and hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:209782

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?
Genetic Background	B6.Cg-Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Tg(APPSwe,tauP301L)1Lfa mutation (3 available)

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

behavior/neurological

abnormal behavior ( J:170670 )

• mutants attend less accurately to short, spatially unpredictable stimuli when the attentional demand of the task is high and also show a general tendency to make more perseverative responses than wild-type mice

• mutants initially respond as accurately as wild-type mice, however subsequently they fail to sustain their attention over the duration of the task, indicating reduced vigilance, or ability to sustain attention over a long period of time

• treatment of mice with the cholinesterase inhibitor donepezil results in an enhanced ability to sustain attention

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:170670

Allelic Composition	App^tm1Ck/App^tm1Ck Psen1^tm1Mpm/Psen1^tm1Mpm
Genetic Background	involves: 129 * 129S1/Sv * 129X1/SvJ

Find Mice

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

nervous system

amyloid beta deposits ( J:166379 )

• mice exhibit decreased amyloid load compared with App^tm3.1Zhe Psen1^tm1Mpm double homozygotes

abnormal brain morphology ( J:191170 )

• corticotropin releasing factor levels are increased in the lateral dorsal bed nucleus of the stria terminalis and the paraventricular nucleus

homeostasis/metabolism

amyloid beta deposits ( J:166379 )

• mice exhibit decreased amyloid load compared with App^tm3.1Zhe Psen1^tm1Mpm double homozygotes

increased circulating corticosterone level ( J:191170 )

• mice exhibit an increase in resting levels of circulating corticosterone

behavior/neurological

enhanced contextual conditioning behavior ( J:191170 )

• mice show increased freezing in the context in which they received the shock compared to wild-type mice but show similar levels of freezing as wild-type mice in cued fear (in response to sound), indicating increased contextual fear

• however, hot plate assay shows normal nociception

abnormal spatial working memory ( J:191170 )

• in the alternation T-maze test, mice show decreased alternation, indicating reduced working memory

increased anxiety-related response ( J:191170 )

• in the elevated plus maze, mice spend more time in the closed arms and less time in the open arms and make fewer entries into the open arms and navigate less distance on the open arms, indicating increased levels of anxiety

• in the light-dark box test, mice spend more time in the closed portion of the box and less time in the open side, make fewer entries to the light side of the box, and spend on average more time on each visit to the dark side, suggesting an increase in hiding behavior and reduction in exploring

• mice show increased freezing in the context in which they received the shock compared to wild-type mice but show similar levels of freezing as wild-type mice in cued fear (in response to sound)

• during the cued trial, mice show increased baseline freezing levels in the 3 minutes before presentation of sound, however increased baseline freezing is not seen before mice are shocked

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:191170

Allelic Composition	Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/0 Tg(Thy1-YFP)HJrs/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cx3cr1^tm1Litt mutation (6 available); any Cx3cr1 mutation (45 available)
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Tg(APPSwe,tauP301L)1Lfa mutation (3 available)
Tg(Thy1-YFP)HJrs mutation (3 available)

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

nervous system

nervous system phenotype ( J:159680 )

N	• mice do not exhibit the neuron loss or increase in microglial density and migration velocity observed in Cx3cr1^tm1Litt/Cx3cr1⁺ Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

Allelic Composition	Cx3cr1^tm1Litt/Cx3cr1⁺ Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/0 Tg(Thy1-YFP)HJrs/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

Find Mice

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

nervous system

abnormal microglial cell morphology ( J:159680 )

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

abnormal microglial cell physiology ( J:159680 )

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

neuron degeneration ( J:159680 )

• of YFP+ layer III neurons at 4 to 6 months

immune system

abnormal microglial cell morphology ( J:159680 )

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

abnormal microglial cell physiology ( J:159680 )

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

hematopoietic system

abnormal microglial cell morphology ( J:159680 )

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

abnormal microglial cell physiology ( J:159680 )

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

Allelic Composition	App^tm3.1Zhe/App^tm3.1Zhe Psen1^tm1Mpm/Psen1^tm1Mpm
Genetic Background	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
App^tm3.1Zhe mutation (0 available); any App mutation (105 available)
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)

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

Amyloid beta deposits in App^tm3.1Zhe/App^tm3.1Zhe Psen1^tm1Mpm/Psen1^tm1Mpm mice

nervous system

amyloid beta deposits ( J:166379 )

• mice exhibit increased amyloid load compared with App^tm1Ck Psen1^tm1Mpm double homozygotes

homeostasis/metabolism

amyloid beta deposits ( J:166379 )

• mice exhibit increased amyloid load compared with App^tm1Ck Psen1^tm1Mpm double homozygotes

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Tg(APPSwe,tauP301L)1Lfa mutation (3 available)

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

behavior/neurological

abnormal learning/memory/conditioning ( J:99604 )

• in Morris water mazed, learning of task is normal but retention is impaired; 6-month old mice require 6 days of training to achieve escape latency of >20 seconds, compared to 3 days in 2 month old control mice

• at 4 and 6 months, mice show longer escape latencies in the first daily trial relative to the last trial of the previous training day indicating day-to-day retention impairment; 2-month old mice do not show this impairment in retention

• short- (1.5 hr posttraining) and long-term (24 hr posttraining) spatial recognition memory in probe trials are impaired at 6 months, whereas 4-month old mice show similar performance at 1.5 hours and impaired retention at 24 hours

• after clearance of intraneuronal Abeta using antibodies, early retention deficits are ablated, whereas long-term retention remains impaired

abnormal contextual conditioning behavior ( J:99604 )

• at 6 months, naive and trained mice display significantly impaired long- and short-term retention for contextual fear; at 4 months, mice have normal retention for short-term (1.5 hr) contextual fear but impaired memory of contextual fear at 24 hours

nervous system

amyloid beta deposits ( J:99604 )

• at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons

• prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation

• treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

homeostasis/metabolism

amyloid beta deposits ( J:99604 )

• prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation

• treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:99604

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/?
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Tg(APPSwe,tauP301L)1Lfa mutation (3 available)

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

nervous system

amyloid beta deposits ( J:107286 )

• Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months

• intraneuronal oligomers are detected at 4-6 months of age

neurofibrillary tangles ( J:107286 )

• tau pathology is detected initially by 6 months of age, and tangle pathology is advanced by 20 months

homeostasis/metabolism

amyloid beta deposits ( J:107286 )

• Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months

• intraneuronal oligomers are detected at 4-6 months of age

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Tg(APPSWE)2576Kha mutation (5 available)

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

nervous system

amyloid beta deposits ( J:175901 )

• mice accumulate more plaques than in Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha mice

homeostasis/metabolism

amyloid beta deposits ( J:175901 )

• mice accumulate more plaques than in Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha mice

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