Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Michael K Ahlijanian, Pfizer Central Research
These transgenic animals display a robust expression of the amino terminal proteolytic fragment p25 of human CDK5R1. Expression is detected in the amygdala, thalamus/hypothalamus, cerebral cortex, and cerebellum. The p25 fragment acts as a positive allosteric regulator of cyclin-dependent kinase 5 (Cdk5), a kinase known to phosphorylate the microtubule-binding protein tau. A two-fold increase in the catalytic activity of Cdk5 is observed in these mice. In contrast to wildtype control mice, brains from 4-month-old exhibit the presence of tau and neurofilament phosphoepitopes. Utlrastructurally, axonal swelling in neurons from the amygdala and spinal cord is observed. Affected neurons possess numerous, abnormally clustered mitochondria and lysosomes, with some evidence of cytoskeletal disorganization. Mice exhibit whole-body tremors at 4-9 weeks of age and enhanced open-field locomotor activity. Aspects of this phenotype are similar to Alzheimer's, Pick's and other neurodegenerative diseases.
|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 016556 B6N.129-Ptpn5tm1Pjlo/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 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)Strains carrying other alleles of CDK5R1View Strains carrying other alleles of CDK5R1 (2 strains)Strains carrying other alleles of Eno2
003834 B6.Cg-Tg(Eno2-Ighmbp2)90Cx Ighmbp2nmd-2J/Cx 003833 B6.Cg-Tg(Eno2-Ighmpb2)17Cx Ighmbp2nmd-2J/Cx 006663 B6.Cg-Tg(Eno2-cre)39Jme/J 003767 B6.Cg-Tg(Eno2tTA)5021Nes/J 003763 B6.Cg-Tg(Eno2tTA)5030Nes/J 012812 B6;D2-Tg(Eno2-MFN2*R94Q)L51Ugfm/J 004360 B6;SJL-Tg(HD)63Aron/J 007857 C57BL/6J-Tg(Eno2-YFP/Cox8a)YRwb/J 007860 C57BL/6J-Tg(Eno2-YFP/Cox8a)ZRwb/J 006297 FVB.Cg-Tg(Eno2-cre)39Jme/J 005938 STOCK Tg(Eno2-cre)39Jme/J 022763 STOCK Tg(Eno2-cre/ERT2)1Pohlk/JView Strains carrying other alleles of Eno2 (12 strains)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
- behavior/neurological phenotype
- abnormal locomotor behavior
- starting at 5-7 weeks of age, mice show increased open-field locomotor activity, which is 2-fold greater than wild-type at 16 weeks (MGI Ref ID J:82825)
- decreased anxiety-related response
- mice show increased open-field locomotor activity, which is 2-fold greater than wild-type at 16 weeks and increased locomotor activity in activity chambers (MGI Ref ID J:82825)
- in elevated-plus maze, mice aged 9-12 weeks spend more time on the open arms compared to wild-type animals (MGI Ref ID J:82825)
- 4-9 week-old mice display whole-body exertion tremors (MGI Ref ID J:82825)
- nervous system phenotype
- abnormal axon morphology
- axonal swelling is observed in neurons in the amygdala and spinal cord of 3- to 6-month old mice; affected axoplasm is filled with numerous abnormally clustered mitochondria and lysosomes, and skeletal components are disorganized (MGI Ref ID J:82825)View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
|Allele Name||transgene insertion 1, John D McNeish|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Common Name(s)||NSE-p25 line A; P25;|
|Mutation Made By||John McNeish, Pfizer Central Research|
|Expressed Gene||CDK5R1, cyclin-dependent kinase 5, regulatory subunit 1 (p35), human|
|Promoter||Eno2, enolase 2, gamma, neuronal, rat|
|General Note||A two-fold increase in the catalytic activity of Cdk5 is observed in transgenic mice. In contrast to wild-type control mice, brains from 4-month-old exhibit the presence of tau and neurofilament phosphoepitopes. Ultrastructurally, axonal swelling in neurons from the amygdala and spinal cord is observed. Affected neurons possess numerous, abnormally clustered mitochondria and lysosomes, with some evidence of cytoskeletal disorganization. Mice exhibit whole-body tremors at 4-9 weeks of age and enhanced open field locomotor activity.|
|Molecular Note||The transgene contains rat enolase 2, gamma neuronal (Eno2) promoter sequence and human cyclin-dependent kinase 5, regulatory subunit 1 sequence (CDK5R1) encoding the amino terminal proteolytic fragment p25. Robust expression of the transgenic fragment 25 is detected in the amygdala, thalamus/hypothalamus, cerebral cortex, and cerebellum. [MGI Ref ID J:82825]|
Ahlijanian MK; Barrezueta NX; Williams RD; Jakowski A; Kowsz KP; McCarthy S; Coskran T; Carlo A; Seymour PA; Burkhardt JE; Nelson RB; McNeish JD. 2000. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5. Proc Natl Acad Sci U S A 97(6):2910-5. [PubMed: 10706614] [MGI Ref ID J:82825]
Noble W; Olm V; Takata K; Casey E; Mary O; Meyerson J; Gaynor K; LaFrancois J; Wang L; Kondo T; Davies P; Burns M; Veeranna; Nixon R; Dickson D; Matsuoka Y; Ahlijanian M; Lau LF; Duff K. 2003. Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38(4):555-65. [PubMed: 12765608] [MGI Ref ID J:130643]
Patrick GN; Zukerberg L; Nikolic M; de la Monte S; Dikkes P; Tsai LH. 1999. Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402(6762):615-22. [PubMed: 10604467] [MGI Ref ID J:93866]
Wen Y; Yu WH; Maloney B; Bailey J; Ma J; Marie I; Maurin T; Wang L; Figueroa H; Herman M; Krishnamurthy P; Liu L; Planel E; Lau LF; Lahiri DK; Duff K. 2008. Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron 57(5):680-90. [PubMed: 18341989] [MGI Ref ID J:132937]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry The donating investigator maintains this strain as a homozygote on a FVB/N background (N6).
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2525.00
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* $3283.00
Cryorecovery - Standard.
Progeny testing is not required.
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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