|In this STEP KO strain, a neo cassette replaces the catalytic site of the protein tyrosine phosphatase, non-receptor type 5 (Ptpn5) gene, abolishing gene expression. These mice may be useful for studying the role of STEP in regulating synaptic plasticity in 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 Generation N10pN1
Donating Investigator Paul Lombroso, Yale University School of Medicine
In this STEP KO strain, a neo cassette replaces the catalytic site of the protein tyrosine phosphatase, non-receptor type 5 (Ptpn5) gene, abolishing gene expression. Homozygotes are viable, fertile, and normal in size. Striatal enriched protein phosphatase (STEP) is a neuron-specific tyrosine phosphatase which regulates synaptic plasticity following glutamatergic and dopaminergic input. Expressed mainly in the striatum, hippocampus, amygdala, and cortex of the brain, glutamate-activated STEP controls synaptic plasticity through limiting the duration of ERK 1/2 MAP kinase activity and by endocytosis of glutamate receptors. Activation of ERK1/2 in STEP-expressing regions of the brain is required for memory formation and learning. STEP levels are also shown to be increased in prefrontal cortex of Alzheimer's Disease (AD) models. Homozygous STEP KO mice lack expression of all STEP isoforms, and exhibit enhanced phosphorylation of ERK1/2 in the striatum, hippocampus, and amygdala, with slight elevation in the lateral septum. Heterozygous mice display a 50% reduction in STEP expression when compared to wildtype littermates. This decrease in STEP levels reverses cognitive and cellular deficits observed in AD mice, and blocks internalization of glutamate receptors. These mice may be useful for studying the role of STEP in regulating synaptic plasticity in Alzheimer's Disease.
A targeting vector was designed to replace 1284 bp of genomic sequence, including the catalytic site, of the protein tyrosine phosphatase, non-receptor type 5 (Ptpn5) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric mice were bred to C57BL/6NCrl mice to generate a colony of STEP KO mice. These mice were backcrossed 10 generations to C57BL/6NCrl background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.
|Considerations for Choosing Controls|
Alzheimer's Disease Models
005987 129-Achetm1Loc/J 006409 129S1.129(Cg)-Tg(APPSw)40Btla/Mmjax 008077 129S1/Sv-Bchetm1Loc/J 016198 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ 014556 129S6/SvEv-Apoetm4Mae/J 006555 A.129(B6)-Tg(APPSw)40Btla/Mmjax 005708 B6.129-Apbb1tm1Quhu/J 004714 B6.129-Bace1tm1Pcw/J 004098 B6.129-Klc1tm1Gsn/J 004193 B6.129-Psen1tm1Mpm/J 003615 B6.129-Psen1tm1Shn/J 005300 B6.129-Tg(APPSw)40Btla/Mmjax 005617 B6.129P-Psen2tm1Bdes/J 002609 B6.129P2-Nos2tm1Lau/J 007685 B6.129P2-Psen1tm1Vln/J 007999 B6.129P2-Sorl1Gt(Ex255)Byg/J 008087 B6.129S1-Bchetm1Loc/J 002509 B6.129S2-Plautm1Mlg/J 005301 B6.129S2-Tg(APP)8.9Btla/J 004163 B6.129S4-Cdk5r1tm1Lht/J 010959 B6.129S4-Grk5tm1Rjl/J 010960 B6.129S4-Grk5tm2Rjl/J 002213 B6.129S4-Ngfrtm1Jae/J 006406 B6.129S4-Tg(APPSwLon)96Btla/Mmjax 006469 B6.129S4-Tg(PSEN1H163R)G9Btla/J 012564 B6.129S5-Dhcr24tm1Lex/SbpaJ 004142 B6.129S7-Aplp2tm1Dbo/J 004133 B6.129S7-Apptm1Dbo/J 007251 B6.129X1-Mapttm1Hnd/J 013040 B6.Cg-Apoetm1Unc Ins2Akita/J 005642 B6.Cg-Clutm1Jakh/J 005491 B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J 009126 B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax 005866 B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax 008730 B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax 005864 B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax 007575 B6.Cg-Tg(CAG-Ngb,-EGFP)1Dgrn/J 016197 B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J 005855 B6.Cg-Tg(Camk2a-Prkaca)426Tabe/J 007004 B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ 004996 B6.Cg-Tg(DBH-Gal)1923Stei/J 007673 B6.Cg-Tg(Gad1-EGFP)3Gfng/J 004662 B6.Cg-Tg(PDGFB-APP)5Lms/J 006293 B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2Mmjax 006006 B6.Cg-Tg(Prnp-APP)A-2Dbo/J 008596 B6.Cg-Tg(Prnp-Abca1)EHol/J 006005 B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/Mmjax 007180 B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J 007182 B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J 005999 B6.Cg-Tg(SBE/TK-luc)7Twc/J 012597 B6.Cg-Tg(Thy1-COL25A1)861Yfu/J 007051 B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax 007052 B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax 007049 B6.Cg-Tg(tetO-APPSwInd)885Dbo/Mmjax 009337 B6.FVB-Tg(Prnp-RTN3)2Yanr/J 006394 B6;129-Apba2tm1Sud Apba3tm1Sud Apba1tm1Sud/J 008364 B6;129-Chattm1(cre/ERT)Nat/J 008476 B6;129-Ncstntm1Sud/J 004807 B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax 007605 B6;129P-Psen1tm1Vln/J 005618 B6;129P2-Bace2tm1Bdes/J 008333 B6;129P2-Dldtm1Ptl/J 002596 B6;129P2-Nos2tm1Lau/J 003822 B6;129S-Psen1tm1Shn/J 012639 B6;129S4-Mapttm3(HDAC2)Jae/J 012869 B6;129S6-Apbb2tm1Her/J 006410 B6;129S6-Chattm2(cre)Lowl/J 005993 B6;129S6-Pcsk9tm1Jdh/J 008636 B6;C-Tg(Prnp-APP695*/EYFP)49Gsn/J 007002 B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax 008169 B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J 000231 B6;C3Fe a/a-Csf1op/J 008850 B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ 003378 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J 004462 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax 003741 B6D2-Tg(Prnp-MAPT)43Vle/J 018957 B6N.129S6(B6)-Chattm2(cre)Lowl/J 024841 B6N.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J 006554 B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax 012621 C.129S(B6)-Chrna3tm1.1Hwrt/J 002328 C.129S2-Plautm1Mlg/J 003375 C3B6-Tg(APP695)3Dbo/Mmjax 005087 C57BL/6-Tg(Camk2a-IDE)1Selk/J 005086 C57BL/6-Tg(Camk2a-MME)3Selk/J 008833 C57BL/6-Tg(Camk2a-UBB)3413-1Fwvl/J 007027 C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax 010800 C57BL/6-Tg(Thy1-PTGS2)300Kand/J 010703 C57BL/6-Tg(Thy1-PTGS2)303Kand/J 005706 C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J 006618 C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J 007677 CB6-Tg(Gad1-EGFP)G42Zjh/J 007072 CByJ.129P2(B6)-Nos2tm1Lau/J 006472 D2.129(B6)-Tg(APPSw)40Btla/Mmjax 007067 D2.129P2(B6)-Apoetm1Unc/J 013719 D2.Cg-Apoetm1Unc Ins2Akita/J 003718 FVB-Tg(GadGFP)45704Swn/J 013732 FVB-Tg(NPEPPS)1Skar/J 013156 FVB-Tg(tetO-CDK5R1*)1Vln/J 015815 FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ 002329 FVB.129S2-Plautm1Mlg/J 003753 FVB/N-Tg(Eno2CDK5R1)1Jdm/J 006143 FVB/N-Tg(Thy1-cre)1Vln/J 008051 NOD.129P2(B6)-Ctsbtm1Jde/RclJ 008390 STOCK Apptm1Sud/J 012640 STOCK Hdac2tm1.2Rdp/J 004808 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J 004779 STOCK Mapttm1(EGFP)Klt/J 014092 STOCK Tg(ACTB-tTA2,-MAPT/lacZ)1Luo/J 014544 STOCK Tg(tetO-ABL1*P242E*P249E)CPdav/JView Alzheimer's Disease Models (109 strains)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.
Ptpn5tm1Pjlo/Ptpn5tm1Pjloinvolves: 129 * C57BL/6
- nervous system phenotype
- *normal* nervous system phenotype
- despite increased MAPK1/3 (ERK1/2) phosphorylation in the brain, development of the brain is normal (MGI Ref ID J:145584)View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Cell Biology Research
Developmental Biology Research
Behavioral and Learning Defects
Channel and Transporter Defects
calcium: glutamate receptor
glutamate receptor: NMDA
|Allele Name||targeted mutation 1, Paul J Lombroso|
|Allele Type||Targeted (Null/Knockout)|
|Mutation Made By||Paul Lombroso, Yale University School of Medicine|
|Strain of Origin||129|
|Gene Symbol and Name||Ptpn5, protein tyrosine phosphatase, non-receptor type 5|
|Gene Common Name(s)||PTPSTEP; STEP;|
|Molecular Note||1284 bp of genomic sequence encoding the catalytic site was replaced with a neo cassette. The absence of protein expression was confirmed by western blot analysis on brain extracts. [MGI Ref ID J:145584]|
Venkitaramani DV; Paul S; Zhang Y; Kurup P; Ding L; Tressler L; Allen M; Sacca R; Picciotto MR; Lombroso PJ. 2009. Knockout of STriatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation. Synapse 63(1):69-81. [PubMed: 18932218] [MGI Ref ID J:145584]
Deb I; Manhas N; Poddar R; Rajagopal S; Allan AM; Lombroso PJ; Rosenberg GA; Candelario-Jalil E; Paul S. 2013. Neuroprotective role of a brain-enriched tyrosine phosphatase, STEP, in focal cerebral ischemia. J Neurosci 33(45):17814-26. [PubMed: 24198371] [MGI Ref ID J:204190]
Goebel-Goody SM; Wilson-Wallis ED; Royston S; Tagliatela SM; Naegele JR; Lombroso PJ. 2012. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. Genes Brain Behav 11(5):586-600. [PubMed: 22405502] [MGI Ref ID J:198038]
Hicklin TR; Wu PH; Radcliffe RA; Freund RK; Goebel-Goody SM; Correa PR; Proctor WR; Lombroso PJ; Browning MD. 2011. Alcohol inhibition of the NMDA receptor function, long-term potentiation, and fear learning requires striatal-enriched protein tyrosine phosphatase. Proc Natl Acad Sci U S A 108(16):6650-5. [PubMed: 21464302] [MGI Ref ID J:171371]
Olausson P; Venkitaramani DV; Moran TD; Salter MW; Taylor JR; Lombroso PJ. 2012. The tyrosine phosphatase STEP constrains amygdala-dependent memory formation and neuroplasticity. Neuroscience 225:1-8. [PubMed: 22885232] [MGI Ref ID J:192490]
Venkitaramani DV; Moura PJ; Picciotto MR; Lombroso PJ. 2011. Striatal-enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory. Eur J Neurosci 33(12):2288-98. [PubMed: 21501258] [MGI Ref ID J:176373]
Xu J; Kurup P; Bartos JA; Patriarchi T; Hell JW; Lombroso PJ. 2012. Striatal-enriched protein-tyrosine phosphatase (STEP) regulates Pyk2 kinase activity. J Biol Chem 287(25):20942-56. [PubMed: 22544749] [MGI Ref ID J:186506]
Zhang Y; Kurup P; Xu J; Carty N; Fernandez SM; Nygaard HB; Pittenger C; Greengard P; Strittmatter SM; Nairn AC; Lombroso PJ. 2010. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A 107(44):19014-9. [PubMed: 20956308] [MGI Ref ID J:166233]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together.
|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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