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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Former Names B6.129-Mapk10tm1Flv (Changed: 15-DEC-04 ) 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 Richard Flavell, Yale University School of Medicine Description
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product, mRNA or protein, is detected in brain tissue. Histological and immunohistological examination of the brains of homozygous mutant mice reveal normal development and cellular organization. Mutant mice are resistant to seizures and neuronal apoptosis caused by administration of excitotoxic glutamate-receptor agonist kainic acid. With higher doses of kainic acid, mutant mice display severe tonic-clonic convulsions, but survive the treatment while wildtype mice have 60% mortality. This mutant mouse strain represents a model that may be useful in studies related to neurotoxicity of excitatory amino acids and induced models of Parkinson's disease and stroke.Development
A targeting vector containing a neomycin resistance gene and a PGK-tk cassette was used to disrupt 1.5 exons of the targeted gene encoding the protein subdomains VIII and IX (amino acid residues 189-267). The construct was electroporated into 129S1 derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (99 strains)
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
assigned by genotype
Mapk10tm1Flv/Mapk10tm1Flv
B6.129S1-Mapk10tm1Flv
- behavior/neurological phenotype
- impaired coordination
- improved performance over controls after treatment with MPTP in a rotorod test but only at low speeds (MGI Ref ID J:87428)
- nervous system phenotype
- abnormal dopamine level
- reduced dopamine levels but not as much as seen in controls after MPTP treatment (MGI Ref ID J:87428)
- abnormal somatic motor system morphology
- decreased susceptibility to dopaminergic neuron neurotoxicity
- increased resistance to MPTP induced Parkinson's disease (MGI Ref ID J:87428)
- homeostasis/metabolism phenotype
- abnormal dopamine level
- reduced dopamine levels but not as much as seen in controls after MPTP treatment (MGI Ref ID J:87428)
- decreased susceptibility to dopaminergic neuron neurotoxicity
- increased resistance to MPTP induced Parkinson's disease (MGI Ref ID J:87428)
- cellular phenotype
- decreased susceptibility to dopaminergic neuron neurotoxicity
- increased resistance to MPTP induced Parkinson's disease (MGI Ref ID J:87428)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Mapk10tm1Flv/Mapk10tm1Flv
involves: 129S1/Sv
- behavior/neurological phenotype
- decreased susceptibility to pharmacologically induced seizures
- resistant to seizures induced by low doses (30mg/kg) of kainic acid (MGI Ref ID J:43658)
- remain sensitive to pentetrazole induced seizures (MGI Ref ID J:43658)
- higher doses of kainic acid (45mg/kg)induced seizures similar to those seen in controls but survival was much better, 60% of controls killed by this dose (MGI Ref ID J:43658)
- nervous system phenotype
- decreased neuron apoptosis
- lower levels of apoptosis (35%) are induced in primary cortical neuron cultures than in wild-type neurons (55%) after 24 hours of treatment with 25 um Abeta25-35 peptide (MGI Ref ID J:124252)
- similar results are obtained for treated cultured hippocampal neurons or cortical neurons treated with Abeta 1-40 (MGI Ref ID J:124252)
- decreased susceptibility to neuronal excitotoxicity
- decreased susceptibility to pharmacologically induced seizures
- resistant to seizures induced by low doses (30mg/kg) of kainic acid (MGI Ref ID J:43658)
- remain sensitive to pentetrazole induced seizures (MGI Ref ID J:43658)
- higher doses of kainic acid (45mg/kg)induced seizures similar to those seen in controls but survival was much better, 60% of controls killed by this dose (MGI Ref ID J:43658)
- cardiovascular system phenotype
- *normal* cardiovascular system phenotype
- exhibit no difference in response to pressure overload compared to wild type exhibit no difference in response to pressure overload compared to wild-type (MGI Ref ID J:108253)
- cellular phenotype
- abnormal cell death
- in mutants, corticospinal neurons are resistant to lesion-induced cell death whereas ~40% of wild-type CSN die after CSN deafferentation at 4 months of age (MGI Ref ID J:117956)
- decreased neuron apoptosis
- lower levels of apoptosis (35%) are induced in primary cortical neuron cultures than in wild-type neurons (55%) after 24 hours of treatment with 25 um Abeta25-35 peptide (MGI Ref ID J:124252)
- similar results are obtained for treated cultured hippocampal neurons or cortical neurons treated with Abeta 1-40 (MGI Ref ID J:124252)
- decreased susceptibility to neuronal excitotoxicity
- homeostasis/metabolism phenotype
- decreased susceptibility to neuronal excitotoxicity
This mouse can be used to support research in many areas including:
Mapk10tm1Flv relatedNeurobiology Research
Parkinson's Disease
resistance to MPTP
Apoptosis Research
Endogenous Regulators
Neurobiology Research
Neurodegeneration
Parkinson's Disease
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Mapk10tm1Flv | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Richard A Flavell | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Jnk3-; | ||
| Mutation Made By | Richard Flavell, Yale University School of Medicine | ||
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| ES Cell Line Name | W9.5/W95 | ||
| ES Cell Line Strain | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| Gene Symbol and Name | Mapk10, mitogen-activated protein kinase 10 | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | C230008H04Rik; JNK3; JNK3A; PRKM10; RIKEN cDNA C230008H04 gene; SAPK/Erk/kinase 2; SAPK1b; SAPKC; SAPb; Serk2; p493F12; p54bSAPK; | ||
| Molecular Note | A neomycin resistance cassette replaced a genomic fragment containing sequences corresponding to amino acids 211-267, which encode the tripeptide dual phosphorylation motif required for protein kinase activity. Northern blot and RT-PCR analysis on totalbrain RNA derived from homozygous mice demonstrated that no detectable transcript is produced from this allele. Enzymatic activity assays on extracts derived from hippocampus of homozygous mice confirmed that no functional protein was expressed from this allele. [MGI Ref ID J:43658] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Mapk10tm1Flv, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Yang DD; Kuan CY; Whitmarsh AJ; Rincon M; Zheng TS; Davis RJ; Rakic P; Flavell RA. 1997. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 389(6653):865-70. [PubMed: 9349820] [MGI Ref ID J:43658]
Additional References
Mapk10tm1Flv relatedAbdelli S; Puyal J; Bielmann C; Buchillier V; Abderrahmani A; Clarke PG; Beckmann JS; Bonny C. 2009. JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis. Diabetologia 52(9):1871-80. [PubMed: 19609503] [MGI Ref ID J:154878]
Barnat M; Enslen H; Propst F; Davis RJ; Soares S; Nothias F. 2010. Distinct roles of c-Jun N-terminal kinase isoforms in neurite initiation and elongation during axonal regeneration. J Neurosci 30(23):7804-16. [PubMed: 20534829] [MGI Ref ID J:160890]
Beffert U; Nematollah Farsian F; Masiulis I; Hammer RE; Yoon SO; Giehl KM; Herz J. 2006. ApoE receptor 2 controls neuronal survival in the adult brain. Curr Biol 16(24):2446-52. [PubMed: 17174920] [MGI Ref ID J:117956]
Brecht S; Kirchhof R; Chromik A; Willesen M; Nicolaus T; Raivich G; Wessig J; Waetzig V; Goetz M; Claussen M; Pearse D; Kuan CY; Vaudano E; Behrens A; Wagner E; Flavell RA; Davis RJ; Herdegen T. 2005. Specific pathophysiological functions of JNK isoforms in the brain. Eur J Neurosci 21(2):363-77. [PubMed: 15673436] [MGI Ref ID J:100808]
Hunot S; Vila M; Teismann P; Davis RJ; Hirsch EC; Przedborski S; Rakic P; Flavell RA. 2004. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A 101(2):665-70. [PubMed: 14704277] [MGI Ref ID J:87428]
Junyent F; de Lemos L; Verdaguer E; Folch J; Ferrer I; Ortuno-Sahagun D; Beas-Zarate C; Romero R; Pallas M; Auladell C; Camins A. 2011. Gene expression profile in JNK3 null mice: a novel specific activation of the PI3K/AKT pathway. J Neurochem 117(2):244-252. [PubMed: 21255018] [MGI Ref ID J:171529]
Keramaris E; Ruzhynsky VA; Callaghan SM; Wong E; Davis RJ; Flavell R; Slack RS; Park DS. 2008. Required roles of Bax and JNKs in central and peripheral nervous system death of retinoblastoma-deficient mice. J Biol Chem 283(1):405-15. [PubMed: 17984095] [MGI Ref ID J:130256]
Keramaris E; Vanderluit JL; Bahadori M; Mousavi K; Davis RJ; Flavell R; Slack RS; Park DS. 2005. c-Jun N-terminal kinase 3 deficiency protects neurons from axotomy-induced death in vivo through mechanisms independent of c-Jun phosphorylation. J Biol Chem 280(2):1132-41. [PubMed: 15528206] [MGI Ref ID J:96192]
Kuan CY; Whitmarsh AJ; Yang DD; Liao G; Schloemer AJ; Dong C; Bao J; Banasiak KJ; Haddad GG; Flavell RA; Davis RJ; Rakic P. 2003. A critical role of neural-specific JNK3 for ischemic apoptosis. Proc Natl Acad Sci U S A 100(25):15184-9. [PubMed: 14657393] [MGI Ref ID J:86985]
Kuan CY; Yang DD; Samanta Roy DR; Davis RJ; Rakic P; Flavell RA. 1999. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 22(4):667-76. [PubMed: 10230788] [MGI Ref ID J:54653]
Liang Q; Bueno OF; Wilkins BJ; Kuan CY; Xia Y; Molkentin JD. 2003. c-Jun N-terminal kinases (JNK) antagonize cardiac growth through cross-talk with calcineurin-NFAT signaling. EMBO J 22(19):5079-89. [PubMed: 14517246] [MGI Ref ID J:85947]
Lu Z; Serghides L; Patel SN; Degousee N; Rubin BB; Krishnegowda G; Gowda DC; Karin M; Kain KC. 2006. Disruption of JNK2 decreases the cytokine response to Plasmodium falciparum glycosylphosphatidylinositol in vitro and confers protection in a cerebral malaria model. J Immunol 177(9):6344-52. [PubMed: 17056565] [MGI Ref ID J:140512]
Morishima Y; Gotoh Y; Zieg J; Barrett T; Takano H; Flavell R; Davis RJ; Shirasaki Y; Greenberg ME. 2001. Beta-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J Neurosci 21(19):7551-60. [PubMed: 11567045] [MGI Ref ID J:124252]
Perier C; Bove J; Wu DC; Dehay B; Choi DK; Jackson-Lewis V; Rathke-Hartlieb S; Bouillet P; Strasser A; Schulz JB; Przedborski S; Vila M. 2007. Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease. Proc Natl Acad Sci U S A 104(19):8161-6. [PubMed: 17483459] [MGI Ref ID J:121592]
Quigley HA; Cone FE; Gelman SE; Yang Z; Son JL; Oglesby EN; Pease ME; Zack DJ. 2011. Lack of neuroprotection against experimental glaucoma in c-Jun N-terminal kinase 3 knockout mice. Exp Eye Res 92(4):299-305. [PubMed: 21272576] [MGI Ref ID J:171823]
Ries V; Silva RM; Oo TF; Cheng HC; Rzhetskaya M; Kholodilov N; Flavell RA; Kuan CY; Rakic P; Burke RE. 2008. JNK2 and JNK3 combined are essential for apoptosis in dopamine neurons of the substantia nigra, but are not required for axon degeneration. J Neurochem 107(6):1578-88. [PubMed: 19014392] [MGI Ref ID J:144751]
Sherrin T; Blank T; Hippel C; Rayner M; Davis RJ; Todorovic C. 2010. Hippocampal c-Jun-N-terminal kinases serve as negative regulators of associative learning. J Neurosci 30(40):13348-61. [PubMed: 20926661] [MGI Ref ID J:165097]
Tachibana H; Perrino C; Takaoka H; Davis RJ; Naga Prasad SV; Rockman HA. 2006. JNK1 is required to preserve cardiac function in the early response to pressure overload. Biochem Biophys Res Commun 343(4):1060-6. [PubMed: 16579967] [MGI Ref ID J:108253]
Yu J; Novgorodov SA; Chudakova D; Zhu H; Bielawska A; Bielawski J; Obeid LM; Kindy MS; Gudz TI. 2007. JNK3 Signaling Pathway Activates Ceramide Synthase Leading to Mitochondrial Dysfunction. J Biol Chem 282(35):25940-9. [PubMed: 17609208] [MGI Ref ID J:124655]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.Colony Maintenance
Breeding & Husbandry This strain originated on a B6;129S1 background, has been backcrossed for more than 5 generations on the C57BL/6 background and may be maintained as a homozygote.
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 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.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
- Cryorecovery - Standard.
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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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 |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 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.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
- Cryorecovery - Standard.
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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
- Genomic DNA is available for this strain from the Mouse DNA Resource.
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering Information
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