Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. However, the donating investigator reports that reproductive performance is poor for unknown reasons. No gene product (mRNA or protein) is detected by Northern blot analysis of liver and kidney or Western blot analysis of peritoneal macrophages. Mutant mice exhibit an impaired type I cytokine immune response with reduced induced interferon gamma production. Macrophages from mutant mice have a reduced p39 MAPK activation and IL-12 production when challenged with LPS lipopolysaccharide). Dendritic cells also have reduced IL-12 production response. Mutant mouse embryo fibroblasts (MEF) have a reduced cytokine expression response to tumor necrosis factor (TNF). This mutant mouse strain may be useful in studies of inflammatory response.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 8 and 9. The construct was electroporated into 129S1/Sv-p+ Tyr+ Kitl+ derived W9.5 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6N mice for at least 10 generations. Upon arriving at The Jackson Laboratory, the mice were crossed with C57BL/6J at least once to establish the colony.SNP (single nucleotide polymorphism) analysis performed by The Jackson Laboratory revealed that this strain is a mixed genetic background (5 out of 27 markers were segregating for non-C57BL/6 alleles).
|Allele Name||targeted mutation 1, Richard A Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||MKK3 KO; Mkk3-|
|Gene Symbol and Name||Map2k3, mitogen-activated protein kinase kinase 3|
|Gene Synonym(s)||AW212142; MAP kinase kinase 3; MAPKK3; MEK3; MKK3; Mek3; Mkk3; PRKMK3; Prkmk3; Prkmk3; SAPKK-2; SAPKK2; expressed sequence AW212142; protein kinase, mitogen-activated, kinase 3|
|Strain of Origin||129S1/Sv-Oca2<+> Tyr<+> Kitl<+>|
|General Note||Homozygous mutant mice are viable and appear normal, healthy, and fertile with no defects in lymphocyte development (thymocytes, splenocytes, and bone-marrow derived dendritic cells). Compared to control sibs, however, macrophages and primary embryonic fibroblasts from mutant mice show reduced activation of p38 MAPK. Cytokine IL-12 (encoded for by Il12a and Il12b) is strongly reduced in mutant macrophages and dendritic cells. Mutant fibroblasts have a defective response to Tnf. Mutant mice also have defective T-helper cells with respect to the ability to produce Ifng in response to antigen stimulation of keyhole limpet hemocyanin (KLH) both in vitro and in vivo (J:54078, J:54309).|
|Molecular Note||A neomycin resistance cassette replaced a 1.5kb region that includes exons 8 and 9, which encode amino acids 217-221 of the protein. This region includes the sequences containing the dual phosphorylation sites (serine and threonine) that are required for activation of the protein. Northern blot and Western blot analyses did not detect expression from this allele in homozygous mutant mice.|
When maintaining a live colony, these mice are bred as homozygotes. The donating investigator reports that reproductive performance is poor for unknown reasons.
|Please inquire about possible genotypes.|
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.
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.
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