B6.129X1-Mpo^tm1Lus/J

Stock number: 004265
Product name: MPO KO
Research areas: Cancer Research, Cardiovascular Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Metabolism Research, Research Tools

Description

Mutant mice display impaired fungicidal activity due to myeloperoxidase deficiency. Under hyperlipidemic conditions, mutant mice develop larger atherosclerotic lesions than control mice. These mice are useful for studying systemic inflammatory defenses against pathogens.

Detailed description

Mice that are homozygous null for the targeted gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Mpo gene product (mRNA or protein) is detected. Mutant mice exhibit total white blood cell counts and differentials similar to wildtype mice. Neutrophils and monocytes in periperhal blood and bone marrow have no endogenous peroxidase activity. Superoxide production levels in peritoneal exudate cells of mutant mice are similar to levels found in wildtype mice. Hypochlorous acid production is undetectable in both isolated leukocytes and peritoneal exudate cells. Mutant mice display impaired fungicidal activity due to myeloperoxidase deficiency. When maintained under hyperlipidemic conditions, mutant mice develop atherosclerotic lesions 50% larger than those seen in control mice.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the targeted gene encoding exon 7. The targeting vector was constructed to insert a premature stop codon at the end of the light chain of the myeloperoxidase enzyme. The construct was electroporated into 129X1/SvJ derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice using a marker-assisted protocol.



A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 43 markers, on Chromosome 15, was segregating with 129.

Allele

Symbol: Mpo^tm1Lus
Name: targeted mutation 1, Aldons J Lusis
MGI accession ID: MGI:2385836
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Mpo
Marker name: myeloperoxidase
Chromosome: 11
Strain of origin: 129X1/SvJ
Molecular note: Exon 7, which includes sequence involved in heme binding, was disrupted by the insertion of a neomycin selection cassette and a premature stop codon, which precludes the translation of sequence encoding the heavy chain. Northern and Western blot analyses of bone marrow confirmed the absence of transcript and protein in homozygous mutant mice.