Description

Strain Information

Former Names C57BL/6J-Ncf1m1J/J    (Changed: 08-DEC-05 ) Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Sibling x Sibling         (Female x Male) Species laboratory mouse Generation N3F4N1F1 (21-NOV-06)

Description
Peritoneal neutrophils and macrophages, bone marrow cells and neutrophils isolated from bone marrow of mice homozygous for Ncf1^m1J fail to produce superoxide upon stimulation in vitro with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA), as determined by kinetic spectrophotometric analysis of cytochrome c reduction. Western blot analysis detected no full-length NCF1/p47^phox protein in cells from these mice; a faint band of slightly smaller molecular size than the wild type NCF1 protein was observed on probing with antibodies to NCF1. To exclude the possibility that the NCF1 protein is produced in cells of mutant mice but is degraded rapidly by endogenous proteases, bone marrow cells were isolated and samples prepared for western blot analysis in the presence of diisopropyl fluorophosphate (DFP); no difference was observed upon analysis of freshly prepared cell lysates made with and without DFP, indicating that NCF1 protein is not expressed in mutant cells (Huang et al. 2000).

Analysis for other NADPH oxidases involved in neutrophil superoxide production revealed that NCF2/p67^phox was present at wild type levels and CYBB/gp91^phox and CYBA/p22^phox were expressed at higher than wild type levels. Other neutrophil products wereassayed and found not to differ in bone marrow cells of C57BL/6J vs. mutant mice: GR-1, a granulocyte marker present on approximately 40% of marrow cells by fluorescence activated cell sorting (FACS) analysis; NCF4/p40^phox and RAC1/RAC2 proteins, analyzed by western blot analysis; and expression of mRNAs encoding the granule proteins myeloperoxidase, elastase, cathepsin, lysozyme, lactoferrin and gelatinase as detected by reverse transcriptase - polymerase chain reaction (RT-PCR) (Huang et al. 2000).

The response of Ncf1^m1J/Ncf1^m1J mice to infectious or irritant (inflammatory stimulus) challenge has not been investigated (Huang et al. 2000). However, mice homozygous for the targeted mutation Ncf1^tm1Shl - which disrupts the gene near the point of the Ncf1^m1J mutation and, like the latter, results in failure of phagocytes to generate a superoxide burst following PMA stimulation in vitro - developed spontaneous infections with a variety of microorganisms including Staphylococcus xylosus, Lactobacillus, a hyaline septate mold and the fungus Paecilomyces, despite being maintained under specific pathogen free conditions. Ten-fold more Staphyloccoccus aureus bacteria survived intracellularly following in vitro uptake by phagocytes inblood from these mice than from control littermates, demonstrating a defect in the intracellular bactericidal activity of the mutant mice. Following intraperitoneal injection of the sterile irritant thioglycolate, twice as many leukocytes were recruited to the peritoneal cavities of Ncf1^tm1Shl homozygous mice than of littermate controls; proportions of neutrophils in mutant and control exudates were similar (Jackson et al., J Exp Med 182:751-758 1995).

Development
This spontaneous mutation arose in the B6.Cg-m +/+ Lepr^db/J (Stock #000697) production colony at The Jackson Laboratory. The mutation was identified in 1999. (Huang CK, et al, 2000) The mutations Lepr^db and m have been selectively bred out of this strain by crossing to C57BL/6J at least three times.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Positive, Type I - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ncf1^m1J/Ncf1^m1J

        B6.Cg-m +/+ Lepr^db/J

• immune system phenotype
• abnormal macrophage physiology (MGI Ref ID J:83428)
  • peritoneal macrophages fail to produce superoxide upon stimulation in vitro with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA)
• impaired granulocyte bactericidal activity (MGI Ref ID J:83428)
  • peritoneal neutrophils, bone marrow cells and neutrophils isolated from bone marrow fail to produce superoxide upon stimulation in vitro with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA)

View Research Applications

Research Applications

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

Ncf1^m1J related

Hematological Research
Immunological Defects
Neutrophil Defects (NADPH oxydase deficiency)

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

Mouse/Human Gene Homologs
granulomatous disease, chronic, autosomal cytochrome-b-positive form 1 (CGD)

Research Tools
Immunology and Inflammation Research (neutrophil NADPH oxydase deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ncf1m1J
Allele Name		mutation 1 Jackson
Allele Type		Spontaneous
Common Name(s)		p47-; p47phox;
Strain of Origin		B6.Cg-m +/+ Leprdb/J
Gene Symbol and Name		Ncf1, neutrophil cytosolic factor 1
Chromosome		5
Gene Common Name(s)		NADPH oxidase subunit (47kDa); NOXO2; Ncf-1; SH3PXD1C; meutrophil cytosolic factor 1; p47phox; p47phox;
Molecular Note		The mutation is an A to C transversion at -2 position at the 5' end of exon 8 of the Ncf1 gene, resulting in aberrant splicing of the Ncf1 transcript. Immunoblotting detected no intact NCF1 protein in cells from these mice.

Genotyping

Genotyping Information

Genotyping Protocols

Ncf1^m1J, PYRO, vers. 2
Ncf1^m1J, REST, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Huang CK; Zhan L; Hannigan MO; Ai Y; Leto TL. 2000. P47(phox)-deficient NADPH oxidase defect in neutrophils of diabetic mouse strains, C57BL/6J-m db/db and db/+. J Leukoc Biol 67(2):210-5. [PubMed: 10670582]  [MGI Ref ID J:83428]

Additional References

Hultqvist M; Olofsson P; Holmberg J; Backstrom BT; Tordsson J; Holmdahl R. 2004. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci U S A 101(34):12646-51. [PubMed: 15310853]  [MGI Ref ID J:92437]

Ncf1^m1J related

Chiriac MT; Roesler J; Sindrilaru A; Scharffetter-Kochanek K; Zillikens D; Sitaru C. 2007. NADPH oxidase is required for neutrophil-dependent autoantibody-induced tissue damage. J Pathol 212(1):56-65. [PubMed: 17380558]  [MGI Ref ID J:122096]

Dietlin TA; Hofman FM; Lund BT; Gilmore W; Stohlman SA; van der Veen RC. 2007. Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion. J Leukoc Biol 81(5):1205-12. [PubMed: 17307863]  [MGI Ref ID J:121711]

Goldmann O; von Kockritz-Blickwede M; Holtje C; Chhatwal GS; Geffers R; Medina E. 2007. Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program. Infect Immun 75(8):4148-57. [PubMed: 17526748]  [MGI Ref ID J:123374]

Hultqvist M; Olofsson P; Holmberg J; Backstrom BT; Tordsson J; Holmdahl R. 2004. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci U S A 101(34):12646-51. [PubMed: 15310853]  [MGI Ref ID J:92437]

Suh SW; Gum ET; Hamby AM; Chan PH; Swanson RA. 2007. Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase. J Clin Invest 117(4):910-8. [PubMed: 17404617]  [MGI Ref ID J:121255]

Yao H; Edirisinghe I; Yang SR; Rajendrasozhan S; Kode A; Caito S; Adenuga D; Rahman I. 2008. Genetic ablation of NADPH oxidase enhances susceptibility to cigarette smoke-induced lung inflammation and emphysema in mice. Am J Pathol 172(5):1222-37. [PubMed: 18403597]  [MGI Ref ID J:134306]

Zhang W; Wang T; Pei Z; Miller DS; Wu X; Block ML; Wilson B; Zhang W; Zhou Y; Hong JS; Zhang J. 2005. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J 19(6):533-42. [PubMed: 15791003]  [MGI Ref ID J:105146]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Mating System	Sibling x Sibling         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

 

This strain is currently This strain is currently on HOLD - Contact Customer Service for more information..
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Pricing

Supply Details

Standard Supply	This strain is currently on HOLD - Contact Customer Service for more information.
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection.

Control Information

	Control
	000664 C57BL/6J	(approximate)
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

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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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