Psen1<tm1Mpm> Targeted Allele Detail MGI Mouse (MGI:1930937)

Psen1^tm1Mpm
Targeted Allele Detail

Nomenclature

Symbol:	Psen1^tm1Mpm
Name:	presenilin 1; targeted mutation 1, Mark P Mattson
MGI ID:	MGI:1930937
Synonyms:	PS-1 M146V KI, PS1KI, PS1M146V, PS1M146VKI^-
Gene:	Psen1 Location: Chr12:85029513-85076149 bp, + strand Genetic Position: Chr12, 37.0 cM

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:51950
Parent Cell Line:	R1 (ES Cell)
Strain of Origin:	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺

Mutation
description

Allele Type:	Targeted (knock-in)
Mutations:	Insertion, Nucleotide substitutions
	Point mutations were introduced into the coding region of exon 5 that altered the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively. A lox-P flanked neomycin cassette was also introduced into exon 4. F2 mice exhibited the expected polymorphism of the targeted allele when genomic DNA was amplified with exon 5 specific primers and the products were digested with the appropriate restriction enzyme. Northern blot analysis of total brain RNA using a Psen1 specific antibody showed that the targeted allele was expressed at normal physiological levels in homozygous mutant mice. (J:51950)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 2 strains available Cell Lines: 0 lines available
Carrying any Psen1 Mutation:	17 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	ht2	tg3	tg4
behavior/neurological		N	√	√
behavior/neurological phenotype		N
abnormal learning/ memory				√
abnormal contextual conditioning behavior			√	√
		hm1	ht2	tg3	tg4
homeostasis/metabolism		√
increased susceptibility to neuronal excitotoxicity		√
		hm1	ht2	tg3	tg4
nervous system		√	√	√	√
increased susceptibility to neuronal excitotoxicity		√
neurodegeneration		√
abnormal neurogenesis			√
amyloid beta deposits				√	√
neurofibrillary tangles					√
		hm1	ht2	tg3	tg4
other phenotype				√	√
amyloid beta deposits				√	√

		hm1	ht2	tg3	tg4
Disease Models		√	√	√
Alzheimer Disease 3		√	√
Alzheimer Disease; AD		√	√	√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

hm1 Disease Model

Psen1^tm1Mpm/Psen1^tm1Mpm

involves: 129S1/Sv * 129X1/SvJ * C57BL/6

ht2 Disease Model

Psen1^tm1Mpm/Psen1^tm1Pcw

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6

tg3 Disease Model

Psen1^tm1Mpm/Psen1^tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa

involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurologicalabnormal learning/ memory (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 systemamyloid 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

other phenotypeamyloid 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	Note	Ref(s)
Models with phenotypic similarity to human diseases not associated with human PSEN1.
Alzheimer Disease; AD		J:99604
Models involving transgenes or other mutation types.¹
Alzheimer Disease; AD		J:99604

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

tg4

Psen1^tm1Mpm/Psen1^tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
Mouse Models of Human Disease	Note		Allelic Composition	Genetic Background	Ref(s)
Models with phenotypic similarity to human diseases associated with human PSEN1.
Alzheimer Disease 3 OMIM ID: 607822		ht2	Psen1^tm1Mpm/Psen1^tm1Pcw	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	J:91277
Alzheimer Disease 3 OMIM ID: 607822		hm1	Psen1^tm1Mpm/Psen1^tm1Mpm	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	J:51950
Models with phenotypic similarity to human diseases not associated with human PSEN1.
Alzheimer Disease; AD OMIM ID: 104300		ht2	Psen1^tm1Mpm/Psen1^tm1Pcw	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	J:91277
		tg3	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	J:99604
		hm1	Psen1^tm1Mpm/Psen1^tm1Mpm	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	J:51950
Models involving transgenes or other mutation types.¹
Alzheimer Disease; AD OMIM ID: 104300		tg3	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	J:99604

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

References

Original:	J:51950 Guo Q et al., "Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice." Nat Med 1999 Jan;5(1):101-6
All:	52 reference(s)

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