Search Criteria: Research Area is "Neurobiology Research: Alzheimer's Disease: Presenilin mutants"

JAX® Mice Strains

Stock
Number
Strain Name
 
Strain Description
Standard Supply
005866 B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax
Repository- Live
Double transgenic mice are viable and fertile. At 6 months of age, double-transgenic mice show visible amyloid plaque deposition but are indistinguishable from nontransgenic animals in all cognitive measures. By 18 months, amyloid deposits were much higher in APPswe/PS1dE9 mice with statistically significant but mild decreases in cholinergic markers (cortex and hippocampus) and somatostatin levels (cortex). Performance of older double-transgenic mice is impaired in all cognitive tasks, and deficits in episodic-like memory tasks correlate with total amyloid-beta peptide loads in the brain. Mutant mice, hemizygous for each transgene, and on the C57BL/6J background (N6), have altered EEG (decreased cortical theta activity and increased beta and gamma activity). EEG differences are detected as early as 7 month of age (Wang et al. Brain Res 2002).
008730 B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
Repository- Live
Hemizygous mice are viable and fertile. These 5XFAD transgenic mice overexpress both mutant human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations and human PS1 harboring two FAD mutations, M146L and L286V. Expression of both transgenes is regulated by neural-specific elements of the mouse Thy1 promoter to drive overexpression in the brain. Mice from this founder line have high APP expression correlating with high burden and accelerated accumulation of the 42 amino acid species of beta-amyloid (Aβ-42). 5XFAD mice generate Aβ-42 almost exclusively and rapidly accumulate massive cerebral levels. On the B6SJL F1 genetic background (see MMRRC stock 34840), intraneuronal Abeta;-42 accumulation is observed starting at 1.5 months of age, just prior to amyloid deposition and gliosis, which begins at two months of age. On a congenic C57BL/6 .....
For more information please see the full phenotype on the strain data sheet
005864 B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Repository- Live
Double transgenic mice express a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) both directed to CNS neurons. Both mutations are associated with early-onset Alzheimer's disease. The “humanized” Mo/HuAPP695swe transgene allows the mice to secrete a human A-beta peptide. Both the transgenic peptide and holoprotein can be detected by antibodies specific for human sequence within this region (Signet Laboratories' monoclonal 6E10 antibody). The included Swedish mutations (K595N/M596L) elevate the amount of A-beta produced from the transgene by favoring processing through the beta-secretase pathway. This “humanized” Mo/HuAPP695swe protein is immunodetected in whole brain protein homogenates. The transgenic mutant human presenilin protein (PS1-dE9), which in high levels displaces detectable endogenous mouse protein, is also immunodetected in whole brain protein homogenates. The donating investigator reports tra .....
For more information please see the full phenotype on the strain data sheet
004807 B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax
Repository- Live
Mice homozygous for all three mutant alleles (3xTg-AD; homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)) are viable, fertile and display no initial gross physical or behavioral abnormalities. Translation of the overexpressed transgenes appears to be restricted to the central nervous system, notably in Alzheimer's disease-relevant areas including the hippocampus and cerebral cortex. A progressive increase in amyloid beta peptide deposition is observed, with intracellular immunoreactivity being detected in some brain regions as early as 3-4 months. Synaptic transmission and long-term potentiation are demonstrably impaired in mice 6 months of age. Between 12-15 months aggregates of conformationally altered and hyperphosphorylated tau are detected in the hippocampus. This mutant mouse exhibits plaque and tangle pathology associated with synaptic dysfunction, traits similar to those observed in Alzheimer's d .....
For more information please see the full phenotype on the strain data sheet
004462 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Repository- Live
Double transgenic mice express a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) both directed to CNS neurons. Both mutations are associated with early-onset Alzheimer's disease. The "humanized" Mo/HuAPP695swe transgene allows the mice to secrete a human A-beta peptide. Both the transgenic peptide and holoprotein can be detected by antibodies specific for human sequence within this region (Signet Laboratories' monoclonal 6E10 antibody). The included Swedish mutations (K595N/M596L) elevate the amount of A-beta produced from the transgene by favoring processing through the beta-secretase pathway. This "humanized" Mo/HuAPP695swe protein is immunodetected in whole brain protein homogenates. The transgenic mutant human presenilin protein (PS1-dE9), which in high levels displaces detectable endogenous mouse protein, is also immunodetected in whole brain protein homogenates. The donating investigator reports that transgenic mice develo .....
For more information please see the full phenotype on the strain data sheet
006554 B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
Repository- Live
These 5XFAD transgenic mice overexpress both mutant human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) Familial Alzheimer's Disease (FAD) mutations and human PS1 harboring two FAD mutations, M146L and L286V. Expression of both transgenes is regulated by neural-specific elements of the mouse Thy1 promoter to drive overexpression in the brain. Mice from this founder line have high APP expression correlating with high burden and accelerated accumulation of the 42 amino acid species of beta-amyloid (Abeta-42). 5XFAD mice generate Abeta-42 almost exclusively, rapidly accumulating massive cerebral levels. On the B6SJL F1 genetic background (see MMRRC stock 34840, intraneuronal Abeta-42 accumulation is observed starting at 1.5 months of age, just prior to amyloid deposition and gliosis, which begins at two months of age. On a congenic C57BL/6J genetic background (For more information please see the full phenotype on the strain data sheet
024025 B6N(Cg)-Psen1tm1.1(KOMP)Vlcg/J
Under Development - Now Accepting Orders
This strain was generated by the Knockout Mouse Phenotyping Program (KOMP2) at The Jackson Laboratory using embryonic stem cells provided by the International Knockout Mouse Consortium. The Psen1 (presenilin 1) gene encodes an enzyme that regulates amyloid precursor protein (APP) processing and cleavage of Notch receptors. Mutations in Psen1 have been associated with the onset and progression of Alzheimer?s disease. A beta-galactosidase-containing cassette disrupts the Psen1 gene in this strain. Phenotype data is being generated by the JAX KOMP2 program and will be available to the public when complete from the International Mouse Phenotyping Consortium website. For additional information on this mutation, please see the Regeneron Velocigene w .....
For more information please see the full phenotype on the strain data sheet
004193 B6.129-Psen1tm1Mpm/J
Cryopreserved - Ready for recovery
The targeted allele (PS1M146VKI) causes a mutation of the mouse Psen1 gene that results in expression of a presenilin-1 protein with the human familial Alzheimer's disease-linked mutation PS1M146V. The neo cassette was deleted from the targeted allele (using a CMV-Cre transgenic line of mice). Published findings indicate that this alteration should not influence the level of expression of mutant PS1. Northern blot analysis and RT-PCR determined mRNA expression of the targeted mutant allele is normal. Homozygous PS1M146VKI mice produce only the mutant gene product. Mice that express this targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Neurodegeneration seen in wild-type mice caused by excitotoxin kainate treatment is increased and accelerated in this mutant strain. Cultured cells expressing the mutant protein exhibit perturbed neuronal calcium homeostasis. This mutant mouse strain represents a model that may b .....
For more information please see the full phenotype on the strain data sheet
003615 B6.129-Psen1tm1Shn/J
Cryopreserved - Ready for recovery
Presenilin-1 is the major gene responsible for early-onset familial Alzheimer's disease. Mice that are homozygous null for this gene die within minutes after being born. Externally, mice exhibit shortened tails that curve to the right, thickened necks, loose skin and hind limbs that curve towards the midline. Their weight is 15-20% that of wildtype. Gross skeletal malformations and central nervous system abnormalities are observed. Death presumably results from impaired respiratory mechanics due to ribcage deformities. Histological examination indicates that alveoli are marginally expanded. By embryonic day 9.5, there is a drastic reduction in neural progenitor cells. Later, the brain exhibits hemorrhages and symmetric cerebral cavitation. Cavitation occurs primarily in the ventrolateral region of the ventricular zone in the posterior portion of the brain.
005617 B6.129P-Psen2tm1Bdes/J
Cryopreserved - Ready for recovery
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern or Western blot analysis. Alveolar wall thickening, fibrotic deposits, hemorahages in alveoli and airways are observed by histological analysis of lung tissue from homozygotes 3 months of age and older. This mutant mouse strain may be useful in studies of Alzheimer's disease.
006469 B6.129S4-Tg(PSEN1H163R)G9Btla/J
Cryopreserved - Ready for recovery
Mice hemizygous for this "H163R mutant PSEN1 YAC" transgene are viable and fertile, while the donating investigator reports that homozygous mice are non-viable. Semi-quantitative RT-PCR of multiple tissues shows expression of H163R mutant human PSEN1 at levels comparable to that of wildtype mouse PSEN1 (50–70%). In contrast to other PSEN1 transgenic models, tissues from this strain express alternatively spliced human PSEN1 transcripts encoding PSEN1 protein (with or without the tetrapeptide VRSQ) and accumulated an 18-kDa PSEN1 C-terminal fragment as shown by western blots, thus expressing a wide spectrum of different human PSEN1 mRNAs and proteins. When crossed to other FAD transgenic strains (for example Stock No. 005300), this transgene is associated with elevated levels of the 42 amino acid form of amyloid-beta (1–42) in both brain and plasma. These mice may be useful in studying neurological disorders such as Familial Alzheimer’s Disease and Down syndrome.
007605 B6;129P-Psen1tm1Vln/J
Cryopreserved - Ready for recovery
These mice possess loxP sites on either side of exon 7 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these "floxed" mice are bred to mice that express Cre recombinase, resulting offspring can have one of three resulting genotypes (only exon 7 deleted, only the neo selection cassette deleted, or both exon 7 and the neo selection cassette deleted) in the cre-expressing tissue(s). These PS1-floxed mice may be useful in generating conditional knockouts of Presenilin 1 for studying Alzheimer's Disease.

For example, when crossed to a strain expressing Cre recombinase in postnatal neurons (see Stock No. 006143), this mutant mouse strain may be useful in studies of amyloid plaque formation.

003822 B6;129S-Psen1tm1Shn/J
Cryopreserved - Ready for recovery
Presenilin-1 is the major gene responsible for early-onset familial Alzheimer's disease. Mice that are homozygous null for this gene die within minutes after being born. Externally, mice exhibit shortened tails that curve to the right, thickened necks, loose skin and hind limbs that curve towards the midline. Their weight is 15-20% that of wildtype. Gross skeletal malformations and central nervous system abnormalities are observed. Death presumably results from impaired respiratory mechanics due to ribcage deformities. Histological examination indicates that alveoli are marginally expanded. By embryonic day 9.5, there is a drastic reduction in neural progenitor cells. Later, the brain exhibits hemorrhages and symmetric cerebral cavitation. Cavitation occurs primarily in the ventrolateral region of the ventricular zone in the posterior portion of the brain.
003378 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
Cryopreserved - Ready for recovery
These transgenic mice express human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe). The mouse prion protein promoter directs expression of both transgenes. Elevated levels of the AB1-42(43) peptide is detected in brain homogenates. By nine months of age, histological examination of brain tissue reveals numerous amyloid deposits resembling those observed in the brains of patients with Alzheimer's disease (AD). The number of amyloid deposits increases dramatically between the ages of 10 and 12 months. These mice provide a useful model for studying the underlying mechanism of amyloid deposition, a process implicated in AD.

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