Overview

Also Known As: Jnk3-

These Mapk10 knock-out mice exhibit resistance to seizures and neuronal apoptosis caused by administration of excitotoxic glutamate-receptor agonist kainic acid.

Donating Investigator

Dr. Richard A. Flavell, Yale University School of Medicine

Genetic overview

Genetic Background	Generation

Mapk10^tm1Flv

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Mapk10	mitogen-activated protein kinase 10

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Research Applications

Neurobiology Research
Apoptosis Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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.

Selected References

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):865-70PubMed: 9349820 MGI: J:43658

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Genetics

Mapk10^tm1Flv

Allele Symbol: Mapk10^tm1Flv

Allele Name	targeted mutation 1, Richard A Flavell
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Mapk10^tm1Flv; targeted mutation 1, Richard A Flavell
Gene Symbol and Name	Mapk10, mitogen-activated protein kinase 10
Gene Synonym(s)	C230008H04Rik; JNK3A; RIKEN cDNA C230008H04 gene; p493F12; p54bSAPK; Serk2; PRKM10; SAPKC; Serk2; C230008H04Rik; JNK3; SAPb; SAPK1b; SAPK/Erk/kinase 2; Jnk3
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	5
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 total brain 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.
Mutations Made By	Dr. Richard Flavell, Yale University School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Parkinson's Disease
  - resistance to MPTP

Genotype: Mapk10^tm1Flv related

Apoptosis Research
- Endogenous Regulators
Neurobiology Research
- Neurodegeneration
- Parkinson's Disease

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mapk10^tm1Flv/Mapk10^tm1Flv
involves: 129S1/Sv

behavior/neurological phenotype

decreased susceptibility to pharmacologically 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
- remain sensitive to pentetrazole induced seizures
- resistant to seizures induced by low doses (30mg/kg) of kainic acid

mammalian phenotype

cardiovascular system phenotype
- exhibit no difference in response to pressure overload compared to wild type
- Normal - exhibit no difference in response to pressure overload compared to wild-type

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
- similar results are obtained for treated cultured hippocampal neurons or cortical neurons treated with Abeta 1-40

decreased susceptibility to neuronal excitotoxicity
- 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

decreased susceptibility to pharmacologically 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
- remain sensitive to pentetrazole induced seizures
- resistant to seizures induced by low doses (30mg/kg) of kainic acid

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

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
- similar results are obtained for treated cultured hippocampal neurons or cortical neurons treated with Abeta 1-40

decreased susceptibility to neuronal excitotoxicity
- 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

homeostasis/metabolism phenotype

decreased susceptibility to neuronal excitotoxicity
- 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

The following phenotype relates to a compound genotype created using this strain

Genotype: Mapk10^tm1Flv/Mapk10^tm1Flv
B6.129S1-Mapk10

behavior/neurological phenotype

impaired coordination
- improved performance over controls after treatment with MPTP in a rotorod test but only at low speeds

cellular phenotype

decreased susceptibility to dopaminergic neuron neurotoxicity
- increased resistance to MPTP induced Parkinson's disease

homeostasis/metabolism phenotype

abnormal dopamine level
- reduced dopamine levels but not as much as seen in controls after MPTP treatment

decreased susceptibility to dopaminergic neuron neurotoxicity
- increased resistance to MPTP induced Parkinson's disease

nervous system phenotype

abnormal somatic motor system morphology
- 3 fold improvement in neuron survival in the facial motor nucleus after axotomy (37% survive)
- improved neuron survival in dorsal root ganglia as well

decreased susceptibility to dopaminergic neuron neurotoxicity
- increased resistance to MPTP induced Parkinson's disease

References

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):865-70PubMed: 9349820 MGI: J:43658

Additional - Mapk10^tm1Flv related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Mapk10^tm1Flv
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the Jnk3- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004322 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Not-For-Profit & Academic Pricing

Service	Genotype	Price
	Heterozygous or Wildtype for Mapk10<tm1Flv>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Related Products and Services

Frozen Mouse Embryo	B6.129S1-Mapk10<tm1Flv>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S1-Mapk10<tm1Flv>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S1-Mapk10<tm1Flv>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129S1-Mapk10<tm1Flv>/J Frozen Embryos	$3373.50

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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.

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Also Known As: Jnk3-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Mapk10tm1Flv

Allele Symbol: Mapk10tm1Flv

Disease Terms

Research Areas By Genotype

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

Genotype: Mapk10tm1Flv related

Mammalian Phenotype Terms by Genotype

Genotype: Mapk10tm1Flv/Mapk10tm1Flvinvolves: 129S1/Sv

behavior/neurological phenotype

mammalian phenotype

nervous system phenotype

cellular phenotype

homeostasis/metabolism phenotype

Genotype: Mapk10tm1Flv/Mapk10tm1FlvB6.129S1-Mapk10

behavior/neurological phenotype

cellular phenotype

homeostasis/metabolism phenotype

nervous system phenotype

References

Additional - Mapk10tm1Flv related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Not-For-Profit & Academic Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Mapk10^tm1Flv

Allele Symbol: Mapk10^tm1Flv

Genotype: Mapk10^tm1Flv related

Genotype: Mapk10^tm1Flv/Mapk10^tm1Flv
involves: 129S1/Sv

Genotype: Mapk10^tm1Flv/Mapk10^tm1Flv
B6.129S1-Mapk10

Additional - Mapk10^tm1Flv related