|These floxed mutant mice possess loxP sites flanking exon 2 of the Psen1 gene. This strain may be useful for generating conditional mutations in applications related to Alzheimer's disease.|
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Jie Shen, Harvard Med Sch/Brigham Women's Hosp
These mice possess loxP sites on either side of exons 2 and 3 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. Northern blot and RT-PCR analysis of brain tissue from homozygotes reveal gene product (mRNA) transcription levels and size are the same as wildtype. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2 and 3 deleted in the cre-expressing tissues.
A loxP site flanked targeting vector containing hygromycin resistance and thymidine kinase genes under the control of the cytomegalovirus (CMV) promoter was utilized in the construction of this mutant. This selection cassette was inserted into intron 3 of the targeted gene, and another loxP site was inserted into intron 1. This construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells which were transiently transfected with a cytomegalovirus-driven Cre recombinase adenovirus vector to remove the selection cassette. ES cells in which Cre recombination resulted in exons 2 and 3 being flanked by loxP sites (the loxP1, 2/3 locus) were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 39 for generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Considerations for Choosing Controls|
Strains carrying other alleles of Psen1
004193 B6.129-Psen1tm1Mpm/J 003615 B6.129-Psen1tm1Shn/J 007685 B6.129P2-Psen1tm1Vln/J 004807 B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax 007605 B6;129P-Psen1tm1Vln/J 003822 B6;129S-Psen1tm1Shn/J 024025 B6N(Cg)-Psen1tm1.1(KOMP)Vlcg/JView Strains carrying other alleles of Psen1 (7 strains)
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.Acne Inversa, Familial, 3; ACNINV3 (PSEN1)
Alzheimer Disease 3 (PSEN1)
Cardiomyopathy, Dilated, 1u; CMD1U (PSEN1)
Frontotemporal Dementia; FTD (PSEN1)
Pick Disease of Brain (PSEN1)
View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Developmental Biology Research
Behavioral and Learning Defects
|Allele Name||targeted mutation 2, Jie Shen|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Common Name(s)||PS1C; Presenilin 1 floxed; fPS1; fPsen1;|
|Mutation Made By||Jie Shen, Harvard Med Sch/Brigham Women's Hosp|
|Strain of Origin||129S4/SvJae|
|ES Cell Line Name||J1|
|ES Cell Line Strain||129S4/SvJae|
|Gene Symbol and Name||Psen1, presenilin 1|
|Gene Common Name(s)||AD3; Ad3h; FAD; PS-1; PS1; S182; alzheimer disease 3 homolog; presenilin-1;|
|Molecular Note||A single loxP site was inserted into intron 1 and a loxP-flanked hygromycin and thymidine kinase selection cassette was inserted into intron 3. The drug selection cassette was removed in ES cells by transient Cre expression in ES cells prior to the production of mice. The final allele has single loxP sites flanking exons 2 and 3. [MGI Ref ID J:60306]|
Balmaceda V; Cuchillo-Ibanez I; Pujadas L; Garcia-Ayllon MS; Saura CA; Nimpf J; Soriano E; Saez-Valero J. 2014. ApoER2 processing by presenilin-1 modulates reelin expression. FASEB J 28(4):1543-54. [PubMed: 24344333] [MGI Ref ID J:211486]
Beglopoulos V; Sun X; Saura CA; Lemere CA; Kim RD; Shen J. 2004. Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. J Biol Chem 279(45):46907-14. [PubMed: 15345711] [MGI Ref ID J:94484]
Colucci-Guyon E; Niedergang F; Wallar BJ; Peng J; Alberts AS; Chavrier P. 2005. A role for mammalian diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages. Curr Biol 15(22):2007-12. [PubMed: 16303559] [MGI Ref ID J:103693]
Demehri S; Liu Z; Lee J; Lin MH; Crosby SD; Roberts CJ; Grigsby PW; Miner JH; Farr AG; Kopan R. 2008. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol 6(5):e123. [PubMed: 18507503] [MGI Ref ID J:139386]
Dong Z; Yan L; Huang G; Zhang L; Mei B; Meng B. 2014. Ibuprofen partially attenuates neurodegenerative symptoms in presenilin conditional double-knockout mice. Neuroscience 270:58-68. [PubMed: 24699228] [MGI Ref ID J:210440]
Garcia-Ayllon MS; Campanari ML; Montenegro MF; Cuchillo-Ibanez I; Belbin O; Lleo A; Tsim K; Vidal CJ; Saez-Valero J. 2014. Presenilin-1 influences processing of the acetylcholinesterase membrane anchor PRiMA. Neurobiol Aging 35(7):1526-36. [PubMed: 24612677] [MGI Ref ID J:213809]
Huang J; Dattilo LK; Rajagopal R; Liu Y; Kaartinen V; Mishina Y; Deng CX; Umans L; Zwijsen A; Roberts AB; Beebe DC. 2009. FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate. Development 136(10):1741-50. [PubMed: 19369394] [MGI Ref ID J:148019]
Kaufmann MR; Barth S; Konietzko U; Wu B; Egger S; Kunze R; Marti HH; Hick M; Muller U; Camenisch G; Wenger RH. 2013. Dysregulation of hypoxia-inducible factor by presenilin/gamma-secretase loss-of-function mutations. J Neurosci 33(5):1915-26. [PubMed: 23365231] [MGI Ref ID J:193889]
Maraver A; Fernandez-Marcos PJ; Herranz D; Canamero M; Munoz-Martin M; Gomez-Lopez G; Mulero F; Megias D; Sanchez-Carbayo M; Shen J; Sanchez-Cespedes M; Palomero T; Ferrando A; Serrano M. 2012. Therapeutic effect of gamma-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma by derepression of DUSP1 and inhibition of ERK. Cancer Cell 22(2):222-34. [PubMed: 22897852] [MGI Ref ID J:191822]
Maraver A; Tadokoro CE; Badura ML; Shen J; Serrano M; Lafaille JJ. 2007. Effect of presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cells. Blood 110(9):3218-25. [PubMed: 17626841] [MGI Ref ID J:142929]
Nakajima M; Matsuda K; Miyauchi N; Fukunaga Y; Watanabe S; Okuyama S; Perez J; Fernandez-Llebrez P; Shen J; Furukawa Y. 2011. Hydrocephalus and abnormal subcommissural organ in mice lacking presenilin-1 in Wnt1 cell lineages. Brain Res 1382:275-81. [PubMed: 21262207] [MGI Ref ID J:170860]
Nakajima M; Watanabe S; Okuyama S; Shen J; Furukawa Y. 2009. Restricted growth and insulin-like growth factor-1 deficiency in mice lacking presenilin-1 in the neural crest cell lineage. Int J Dev Neurosci 27(8):837-43. [PubMed: 19665542] [MGI Ref ID J:157272]
Ong CT; Sedy JR; Murphy KM; Kopan R. 2008. Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition. PLoS ONE 3(7):e2823. [PubMed: 18665263] [MGI Ref ID J:139496]
Pan Y; Lin MH; Tian X; Cheng HT; Gridley T; Shen J; Kopan R. 2004. gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev Cell 7(5):731-43. [PubMed: 15525534] [MGI Ref ID J:94517]
Rocher-Ros V; Marco S; Mao JH; Gines S; Metzger D; Chambon P; Balmain A; Saura CA. 2010. Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. Oncogene 29(20):2950-61. [PubMed: 20208556] [MGI Ref ID J:168265]
Satpathy AT; Briseno CG; Lee JS; Ng D; Manieri NA; Kc W; Wu X; Thomas SR; Lee WL; Turkoz M; McDonald KG; Meredith MM; Song C; Guidos CJ; Newberry RD; Ouyang W; Murphy TL; Stappenbeck TS; Gommerman JL; Nussenzweig MC; Colonna M; Kopan R; Murphy KM. 2013. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol 14(9):937-48. [PubMed: 23913046] [MGI Ref ID J:208234]
Saura CA; Chen G; Malkani S; Choi SY; Takahashi RH; Zhang D; Gouras GK; Kirkwood A; Morris RG; Shen J. 2005. Conditional inactivation of presenilin 1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic mice. J Neurosci 25(29):6755-64. [PubMed: 16033885] [MGI Ref ID J:99847]
Saura CA; Choi SY; Beglopoulos V; Malkani S; Zhang D; Shankaranarayana Rao BS; Chattarji S; Kelleher RJ 3rd; Kandel ER; Duff K; Kirkwood A; Shen J. 2004. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42(1):23-36. [PubMed: 15066262] [MGI Ref ID J:89760]
Su J; Gu J; Dong Z; Mei B. 2013. Ibuprofen rescues abnormalities in periodontal tissues in conditional presenilin 1 and presenilin 2 double knockout mice. Int J Mol Sci 14(9):18457-69. [PubMed: 24018889] [MGI Ref ID J:202691]
Tabuchi K; Chen G; Sudhof TC; Shen J. 2009. Conditional forebrain inactivation of nicastrin causes progressive memory impairment and age-related neurodegeneration. J Neurosci 29(22):7290-301. [PubMed: 19494151] [MGI Ref ID J:149506]
Wines-Samuelson M; Schulte EC; Smith MJ; Aoki C; Liu X; Kelleher RJ 3rd; Shen J. 2010. Characterization of age-dependent and progressive cortical neuronal degeneration in presenilin conditional mutant mice. PLoS One 5(4):e10195. [PubMed: 20419112] [MGI Ref ID J:160144]
Wu B; Yamaguchi H; Lai FA; Shen J. 2013. Presenilins regulate calcium homeostasis and presynaptic function via ryanodine receptors in hippocampal neurons. Proc Natl Acad Sci U S A 110(37):15091-6. [PubMed: 23918386] [MGI Ref ID J:200916]
Xiong H; Maraver A; Latkowski JA; Henderson T; Schlessinger K; Ding Y; Shen J; Tadokoro CE; Lafaille JJ. 2013. Characterization of two distinct lymphoproliferative diseases caused by ectopic expression of the Notch ligand DLL4 on T cells. PLoS One 8(12):e84841. [PubMed: 24386421] [MGI Ref ID J:209839]
Yu H; Saura CA; Choi S; Sun LD; Yang X; Handler M; Kawarabayashi T; Younkin L; Fedeles B; Wilson MA; Younkin S; Kandel ER; Kirkwood A; Shen J. 2001. App processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron 31(5):713-26. [PubMed: 11567612] [MGI Ref ID J:71606]
Zhang C; Wu B; Beglopoulos V; Wines-Samuelson M; Zhang D; Dragatsis I; Sudhof TC; Shen J. 2009. Presenilins are essential for regulating neurotransmitter release. Nature 460(7255):632-6. [PubMed: 19641596] [MGI Ref ID J:150936]
Zhang D; Zhang C; Ho A; Kirkwood A; Sudhof TC; Shen J. 2010. Inactivation of presenilins causes pre-synaptic impairment prior to post-synaptic dysfunction. J Neurochem 115(5):1215-21. [PubMed: 20854432] [MGI Ref ID J:166955]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry When maintaining a live colony, these mice can be bred as homozygotes.
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2140.00
At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|Pricing for International shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2782.00
Cryorecovery - Standard.
Progeny testing is not required.
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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