B6N.129S2-Ncf1^tm1Shl/J

Stock number: 027331
Product name: p47^phox-
Research areas: Research Tools, Virology Research

Description

p47^phox-/- mice may be useful for studying role of NADPH oxidase in the prevention of and susceptibility to infections.

Detailed description

p47^phox-/- mice contain a neo cassette interrupting exon 7, at amino acid 221, of the neutrophil cytosolic factor 1 (Ncf1) gene, abolishing gene function. Mice homozygous for this allele are viable and fertile. p47^phox is the cytosolic subunit of phagocyte nicotinamide dinucleotide phosphate (NADPH) oxidase, and is required for its activation and subsequent production of superoxide. Superoxide is a toxic oxygen species that has been noted for the oxidative damage it causes during aging and in the development of some autoimmune diseases and cancers. Superoxide is also deployed by the immune system for use in oxygen-dependent killing mechanisms of invading pathogens. Mutations in p47^phox has been linked to the onset of the immunodeficiency syndrome chronic granulomatous disease (CGD) which is characterized by extreme susceptibility to infection.

Homozygous p47^phox-/- mice are susceptible to infections by pathogens such as Staphylococcus spp., Lactobacillus, the Burkholderia cepacia complex, Serratia marcescens, Aspergillus spp., and Nocardia spp. but not Escherichia coli. Following intraperitoneal injection with thiogllycolate, mice exhibit inflammation recruiting twice as many leukocytes as controls. Homozygotes develop lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. Leukocyte numbers and survival in heterozygotes are not significantly different from that seen in wildtype control mice.

 

Development

A targeting vector was designed to insert a neomycin resistance (neo) cassette in reverse orientation to the gene into the 3’ end of exon 7 of the neutrophil cytosolic factor 1 (Ncf1) gene. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6NTac females. p47^phox-/- mice were backcrossed to C57BL/6NTac mice for at least 15 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Ncf1^tm1Shl
Name: targeted mutation 1, Steven M Holland
MGI accession ID: MGI:1934143
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ncf1
Marker name: neutrophil cytosolic factor 1
Chromosome: 5
Strain of origin: 129S2/SvPas
Molecular note: Insertion of a neomycin resistance cassette into exon 7 disrupted the gene. The region in the human ortholog that corresponds to exon 7 is known to be necessary for gene function.