B6.129S1-Mapk10^tm1Flv/J

Stock number: 004322
Product name: Jnk3-
Research areas: Apoptosis Research, Neurobiology Research

Description

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

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.

Allele

Symbol: Mapk10^tm1Flv
Name: targeted mutation 1, Richard A Flavell
MGI accession ID: MGI:2176237
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Mapk10
Marker name: mitogen-activated protein kinase 10
Chromosome: 5
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
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.