Description

Strain Information

Former Names B6.129-Mapk10tm1Flv    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. 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.

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Mapk10^tm1Flv/Mapk10^tm1Flv

        B6.129S1-Mapk10^tm1Flv

• behavior/neurological phenotype
• impaired coordination (MGI Ref ID J:87428)
  • improved performance over controls after treatment with MPTP in a rotorod test but only at low speeds
• nervous system phenotype
• abnormal dopamine level (MGI Ref ID J:87428)
  • reduced dopamine levels but not as much as seen in controls after MPTP treatment
• abnormal dopaminergic neuron morphology (MGI Ref ID J:87428)
  • increased resistance to MPTP induced Parkinson's disease
• abnormal somatic motor system morphology (MGI Ref ID J:96192)
  • 3 fold improvement in neuron survival in the facial motor nucleus after axotomy (37% survive)
  • improved neuron survival in dorsal root ganglia as well

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mapk10^tm1Flv/Mapk10^tm1Flv

        involves: 129S1/Sv

• behavior/neurological phenotype
• increased resistance to pharmacologically induced seizures (MGI Ref ID J:43658)
  • resistant to seizures induced by low doses (30mg/kg) of kainic acid
  • remain sensitive to pentetrazole induced seizures
  • 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
• nervous system phenotype
• decreased neuron apoptosis (MGI Ref ID J:124252)
  • 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
  • similar results are obtained for treated cultured hippocampal neurons or cortical neurons treated with Abeta 1-40
• decreased susceptibility to neuronal excitotoxicity (MGI Ref ID J:43658)
  • resistant to damage seen in pyramidal neurons of CA1 of controls when treated with kainic acid
  • resistant to hippocampal cell damage which is evident at 30mg/kg kainic acid dose in control mice; limited damage seen at a 45mg/kg dos
• increased resistance to pharmacologically induced seizures (MGI Ref ID J:43658)
  • resistant to seizures induced by low doses (30mg/kg) of kainic acid
  • remain sensitive to pentetrazole induced seizures
  • 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
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:108253)
  • exhibit no difference in response to pressure overload compared to wild type exhibit no difference in response to pressure overload compared to wild-type
• cellular phenotype
• abnormal cell death (MGI Ref ID J:117956)
  • 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
• homeostasis/metabolism phenotype
• decreased susceptibility to neuronal excitotoxicity (MGI Ref ID J:43658)
  • resistant to damage seen in pyramidal neurons of CA1 of controls when treated with kainic acid
  • resistant to hippocampal cell damage which is evident at 30mg/kg kainic acid dose in control mice; limited damage seen at a 45mg/kg dos
• increased resistance to pharmacologically induced seizures (MGI Ref ID J:43658)
  • resistant to seizures induced by low doses (30mg/kg) of kainic acid
  • remain sensitive to pentetrazole induced seizures
  • 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

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Parkinson's Disease (resistance to MPTP)

Mapk10^tm1Flv related

Apoptosis Research
Endogenous Regulators

Neurobiology Research
Neurodegeneration
Parkinson's Disease

Genes & Alleles

Gene & Allele Information

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; FLJ12099; FLJ33785; JNK3; JNK3A; MGC50974; PRKM10; RIKEN cDNA C230008H04 gene; SAPK(beta); SAPK/Erk/kinase 2; 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

Mapk10^tm1Flv, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

Mapk10^tm1Flv related

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]

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]

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

Health & Colony Maintenance Information

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, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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.

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Terms of Use

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- Strain(s) not available to companies or for-profit entities.

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phone:	207-288-6470
fax:	207-288-6655

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“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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