These Nlrp1b deficient mice may be useful for studying role of the inflammasome in immune response.
Beverly H Koller, University of North Carolina at Chapel Hill
In this strain, a loxP-flanked neo cassette replaces exons 1-3 of the NLR family, pyrin domain containing 1B (Nlrp1b) gene, abolishing expression. Of note, these mice were developed on a 129 background. 129 mice do not encode functional Nlrp1a and Nlrp1c proteins, therefore, inactivation of the functional Nlrp1b gene is expected to yield an Nlrp1-/- colony. Nlrp1b encodes a pattern recognition receptor that is involved in the formation of the inflammasome which regulates the immune system's response to injury, toxins, and infection by cleaving interleukin (IL)-1β. Nlrp1b is specifically activated upon sensing the anthrax lethal toxin and the resulting release of pro-inflammatory cytokines aids in the clearance of the anthrax infection. Homozygous Nlrp3-deficient mice are viable and fertile. Bone marrow derived macrophages from these Nlrp1b-/- mice are not sensitive to anthrax LT challenge. These mice are able to form the inflammasome and activate caspase-1. Caspase-1 activation in these mice leads to pyroptosis, which results in acute lung injury and morbidity within 3 days of infection.
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. We may modify the strain description if necessary as published results become available.
A targeting vector was designed to replace exons 1-3 of the NLR family, pyrin domain containing 1B (Nlrp1b) gene with a loxP-flanked neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to 129S6/SvEvTac to establish a colony. 129 mice do not encode functional NLRP1A and NLRP1C proteins, therefore, inactivation of the functional Nlrp1b gene is expected to yield an Nlrp1-/- colony. These mice were then bred to C57BL/6J mice for at least 6 generations and still maintain complete Nlrp1-deficiency. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Beverly H Koller|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Nlrp1b, NLR family, pyrin domain containing 1B|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||The coding sequence in exon 1, 2 and 3 was replaced with a floxed neo cassette.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Nlrp1b- mouse strain in a publication, please cite the originating article(s) and include JAX stock #021301 in your Materials and Methods section.