Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N10+N1F1 (07-JUN-07)   Donating Investigator Aldons Lusis,   University of California at Los Angeles

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 wildtypes 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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Mpo^tm1Lus/Mpo^tm1Lus

        B6.129X1-Mpo^tm1Lus

• immune system phenotype
• abnormal neutrophil physiology (MGI Ref ID J:112488)
  • neutrophils exhibit reduced lysis of muscles cells that are superoxide dismutase treated, mechanically loaded muscle cells whereas lysis by wild-type neutrophils is increased
• muscle phenotype
• abnormal muscle fiber morphology (MGI Ref ID J:112488)
  • following an unloading and reloading protocol, muscle fibers exhibit 52% less injury than in wild-type mice and membrane lysis is reduced
• homeostasis/metabolism phenotype
• abnormal response to injury (MGI Ref ID J:112488)
  • following an unloading and reloading protocol, muscle fibers exhibit 52% less injury than in wild-type mice and membrane lysis is reduced

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mpo^tm1Lus/Mpo^tm1Lus

        involves: 129X1/SvJ * C57BL/6J

• life span-post-weaning/aging
• abnormal induced morbidity/mortality (MGI Ref ID J:67586)
  • following infection with Candida, 40% of mice die by day 20 compared to 100% survival of wild-type mice 65 days after infection
  • no mice are alive 5 days after cecal ligation and puncture (CLP) unlike wild-type mice that exhibit 63% survival after 5 days and 38% after 1 week
• immune system phenotype
• abnormal neutrophil physiology (MGI Ref ID J:67586)
  • neutrophils fail to produce hypochlorous acid and to chlorinate proteins in vivo
  • in culture, neutrophils exhibit reduced killing of Candida and more ingested Candida germinate than when ingested by wild-type neutrophils
• decreased inflammatory response (MGI Ref ID J:102688)
  • asbestos-associated inflammation is delayed compared to in wild-type mice
• increased monocyte cell number (MGI Ref ID J:67586)
  • when bone marrow is transplanted into irradiated Ldlr^tm1Her homozygotes, mice fed a high fat, high-cholesterol diet exhibit increased monocyte cells in atherosclerotic lesions compared to Ldlr^tm1Her homozygotes transplanted with wild type bone marrow
• increased susceptibility to experimental autoimmune encephalomyelitis (MGI Ref ID J:102965)
  • 90% of mice develop hind quarter paralysis following exposure to MOG35-55 peptide in complete Freunds adjuvant (CFA) with pertussis toxin compared to 33% of wild-type mice during 30 days of observation
• increased susceptibility to fungal infection (MGI Ref ID J:67586)
  • following infection with Candida, 40% of mice die by day 20 compared to 100% survival of wild-type mice 65 days after infection
  • unlike wild-type mice, following infection with Candida mice exhibit fungal infiltration of the kidneys
• sepsis (MGI Ref ID J:126649)
  • no mice are alive 5 days after cecal ligation and puncture (CLP) unlike wild-type mice that exhibit 63% survival after 5 days and 38% after 1 week
  • however, cellular response to sepsis is normal
• cardiovascular system phenotype
• atherosclerotic lesions (MGI Ref ID J:67586)
  • when bone marrow transplanted into irradiated Ldlr^tm1Her homozygotes, mice fed a high fat, high-cholesterol diet develop 50% larger atherosclerotic lesions than in Ldlr^tm1Her homozygotes transplanted with wild-type bone marrow
• homeostasis/metabolism phenotype
• increased sensitivity to xenobiotics (MGI Ref ID J:102688)
  • asbestos-associated epithelial cell proliferation is increased in the distal bronchioles compared to in wild-type mice
• hematopoietic system phenotype
• increased monocyte cell number (MGI Ref ID J:67586)
  • when bone marrow is transplanted into irradiated Ldlr^tm1Her homozygotes, mice fed a high fat, high-cholesterol diet exhibit increased monocyte cells in atherosclerotic lesions compared to Ldlr^tm1Her homozygotes transplanted with wild type bone marrow

Mpo^tm1Lus/Mpo^tm1Lus

        involves: 129X1/SvJ

• cardiovascular system phenotype
• atherosclerotic lesions (MGI Ref ID J:112270)
  • when bone marrow transplanted into irradiated Ldlr^tm1Her homozygotes, mice fed a high fat diet develop 1.9-fold larger atherosclerotic lesions than in Ldlr^tm1Her homozygotes transplanted with wild-type bone marrow

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cardiovascular Research
Atherosclerosis
Diet-Induced Atherosclerosis (Susceptible)

Hematological Research
Neutrophil Defects

Immunology and Inflammation Research
Immunodeficiency (Neutrophil Defects)
Immunodeficiency (multiple immune defects)
Inflammation (Neutrophil defects)

Research Tools
Hematological Research
Immunology and Inflammation Research (genes regulating susceptibility to infectious disease and endotoxin)

Mpo^tm1Lus related

Cancer Research
Other (tumor metastasis)

Cardiovascular Research
Atherosclerosis

Immunology and Inflammation Research
Inflammation (Neutrophil defects)

Metabolism Research
Free Radical Research

Research Tools
Cancer Research (Mutation Rate Quantitation and Identification)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Mpotm1Lus
Allele Name		targeted mutation 1, Aldons J Lusis
Allele Type		Targeted (knock-out)
Mutation Made By		Aldons Lusis,   University of California at Los Angeles
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Mpo, myeloperoxidase
Chromosome		11
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 that 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. [MGI Ref ID J:67586]

Genotyping

Genotyping Information

Genotyping Protocols

Mpo^tm1Lus, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Brennan ML; Anderson MM; Shih DM; Qu XD; Wang X; Mehta AC; Lim LL; Shi W; Hazen SL; Jacob JS; Crowley JR; Heinecke JW; Lusis AJ. 2001. Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest 107(4):419-30. [PubMed: 11181641]  [MGI Ref ID J:67586]

Additional References

Zhang R; Brennan ML; Shen Z; MacPherson JC; Schmitt D; Molenda CE; Hazen SL. 2002. Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. J Biol Chem 277(48):46116-22. [PubMed: 12359714]  [MGI Ref ID J:80550]

Mpo^tm1Lus related

Brennan M; Gaur A; Pahuja A; Lusis AJ; Reynolds WF. 2001. Mice lacking myeloperoxidase are more susceptible to experimental autoimmune encephalomyelitis. J Neuroimmunol 112(1-2):97-105. [PubMed: 11108938]  [MGI Ref ID J:102965]

Brovkovych V; Gao XP; Ong E; Brovkovych S; Brennan ML; Su X; Hazen SL; Malik AB; Skidgel RA. 2008. Augmented inducible nitric oxide synthase expression and increased NO production reduce sepsis-induced lung injury and mortality in myeloperoxidase-null mice. Am J Physiol Lung Cell Mol Physiol 295(1):L96-103. [PubMed: 18424617]  [MGI Ref ID J:138540]

Gaut JP; Yeh GC; Tran HD; Byun J; Henderson JP; Richter GM; Brennan ML; Lusis AJ; Belaaouaj A; Hotchkiss RS; Heinecke JW. 2001. Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proc Natl Acad Sci U S A 98(21):11961-6. [PubMed: 11593004]  [MGI Ref ID J:126649]

Gusdon AM; Votyakova TV; Mathews CE. 2008. mt-Nd2a suppresses reactive oxygen species production by mitochondrial complexes I and III. J Biol Chem 283(16):10690-7. [PubMed: 18281288]  [MGI Ref ID J:136549]

Haegens A; van der Vliet A; Butnor KJ; Heintz N; Taatjes D; Hemenway D; Vacek P; Freeman BA; Hazen SL; Brennan ML; Mossman BT. 2005. Asbestos-induced lung inflammation and epithelial cell proliferation are altered in myeloperoxidase-null mice. Cancer Res 65(21):9670-7. [PubMed: 16266986]  [MGI Ref ID J:102688]

Kumar AP; Reynolds WF. 2005. Statins downregulate myeloperoxidase gene expression in macrophages. Biochem Biophys Res Commun 331(2):442-51. [PubMed: 15850779]  [MGI Ref ID J:97973]

McMillen TS; Heinecke JW; LeBoeuf RC. 2005. Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation 111(21):2798-804. [PubMed: 15911707]  [MGI Ref ID J:112270]

Nguyen HX; Lusis AJ; Tidball JG. 2005. Null mutation of myeloperoxidase in mice prevents mechanical activation of neutrophil lysis of muscle cell membranes in vitro and in vivo. J Physiol 565(Pt 2):403-13. [PubMed: 15790660]  [MGI Ref ID J:112488]

Ostanin DV; Barlow S; Shukla D; Grisham MB. 2007. NADPH oxidase but not myeloperoxidase protects lymphopenic mice from spontaneous infections. Biochem Biophys Res Commun 355(3):801-6. [PubMed: 17316569]  [MGI Ref ID J:118594]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	This strain originated on a 129X1/SvJ background and has been backcrossed to C57BL/6J for at least ten generations(12/17/01).
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.