This Map3k14 (NIK) knockout strain exhibits abnormal lymphorganogenesis and is useful in studies of the alternative noncanonical NF-kappaB activation pathway.
Robert Schreiber, Washington University School of Medicine
The serine/threonine protein-kinase encoded by the Map3k14 gene interacts with TRAF2 and is involved in the activation of NF-kappa-B. These mice carry a knock-out mutation of the Map3k14 gene in which a NEO cassette replaced a 1.3 kb region containing the first 120 bp of exon 1.
Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (protein) is detected by Western blot analysis of lung, spleen, and kidney tissue from homozygotes. Homozygotes do not develop lymph nodes (cervical, inguinal, mesenteric, popliteal, and axillary lymph nodes are absent) nor Peyer’s patches. Null mice exhibit abnormal spleen and thymus morphology, have an impaired antibody response to immunization, impaired CD8 T cell memory response to acute viral infection, defective IgA class switching (when induced by anti-CD40 and BAFF), and are more susceptible to bacterial eye infections.
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. 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 a NEO cassette was used to disrupt a 1.3 kb region that contained the first 120 bp of exon 1. The construct was electroporated into 129/Sv derived GS1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then backcrossed to C57BL/6NTac for 10 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.
|Allele Name||targeted mutation 1, Robert D Schreiber|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Map3k14, mitogen-activated protein kinase kinase kinase 14|
|Strain of Origin||129/Sv|
|Molecular Note||The gene was disrupted by replacing the first 120 bp of exon 1 with a neomycin resistance cassette. Western blot analysis of lung, spleen, and kidney samples from homozygous mutant animals verified the null allele.|
When maintaining a live colony, these mice can be bred as homozygotes. Homozygous females are poor breeders. Of note, homozygotes are more susceptible to bacterial eye infections.
When using the NIK KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #025557 in your Materials and Methods section.