Overview

Estimated Removal of Live Colony date: 26 March 2020.

Peritoneal neutrophils and macrophages, bone marrow cells and neutrophils isolated from bone marrow of mice homozygous for Ncf1^m1J spontaneous mutation fail to produce superoxide upon stimulation in vitro with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA).

Genetic overview

Genetic Background	Generation
	N3+N3F5 (2020-04-09 00:00:00)

Ncf1^m1J

Allele Type	Gene Symbol	Gene Name
Spontaneous	Ncf1	neutrophil cytosolic factor 1

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Research Applications

Mouse/Human Gene Homologs
Research Tools
Hematological Research
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$236.78 Domestic price for female 4-week

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 were assayed 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 (Stock No. 027331) - 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.BKS(D)-Lepr^db/J (Stock No. 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 Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):210-5PubMed: 10670582 MGI: J:83428

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Genetics

Ncf1^m1J

Allele Symbol: Ncf1^m1J

Allele Name	mutation 1, Jackson
Allele Type	Spontaneous
Allele Synonym(s)	Ncf1*; p47^-; p47^phox; p47phox^-`; rs230824082
Gene Symbol and Name	Ncf1, neutrophil cytosolic factor 1
Gene Synonym(s)
Strain of Origin	B6.Cg-Dock7^m +/+ Lepr^db/J
Chromosome	5
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.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

chronic granulomatous disease

Research Areas By Phenotype

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

Genotype: Ncf1^m1J related

Mouse/Human Gene Homologs
- granulomatous disease, chronic, autosomal cytochrome-b-positive form 1 (CGD)
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - neutrophil NADPH oxydase deficiency
Hematological Research
- Immunological Defects
- Neutrophil Defects
  - NADPH oxydase deficiency
Immunology, Inflammation and Autoimmunity Research
- Inflammation
  - Neutrophil defects
- Immunodeficiency
  - Neutrophil Defects

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Ncf1^m1J/Ncf1^m1J
B6.Cg-Dock7 +/+ Lepr/J

hematopoietic system phenotype

abnormal macrophage physiology
- 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
- 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)

immune system phenotype

abnormal macrophage physiology
- peritoneal macrophages fail to produce superoxide upon stimulation in vitro with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA)

decreased susceptibility to Orthomyxoviridae infection
- following exposure to inactivated H5N1 virus, acute-lung injury is attenuated compared to in wild-type mice

decreased susceptibility to viral infection
- following exposure to inactivated H5N1 virus, acute-lung injury is attenuated compared to in wild-type mice

impaired granulocyte bactericidal activity
- 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)

Genotype: Ncf1^m1J/Ncf1^m1J
involves: C57BL/6

cellular phenotype

oxidative stress
- in the sinoatrial node of STZ-treated mice

References

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):210-5PubMed: 10670582 MGI: 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):12646-51PubMed: 15310853 MGI: J:92437

Additional - Ncf1^m1J related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Restriction Enzyme Digest:Ncf1
- Pyrosequencing:Ncf1
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Mating System
- Homozygote x Homozygote
Citation
When using the B6(Cg)-Ncf1^m1J/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004742 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Ncf1<m1J>

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Frozen Mouse Embryo	B6(Cg)-Ncf1<m1J>/J	$2595.00
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Frozen Mouse Embryo	B6(Cg)-Ncf1<m1J>/J	$3373.50
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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Ncf1m1J

Allele Symbol: Ncf1m1J

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Ncf1m1J related

Mammalian Phenotype Terms by Genotype

Genotype: Ncf1m1J/Ncf1m1JB6.Cg-Dock7 +/+ Lepr/J

hematopoietic system phenotype

immune system phenotype

Genotype: Ncf1m1J/Ncf1m1Jinvolves: C57BL/6

cellular phenotype

References

Additional References

Additional - Ncf1m1J related

Genotyping Protocols

Dietary Information

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ncf1^m1J

Allele Symbol: Ncf1^m1J

Genotype: Ncf1^m1J related

Genotype: Ncf1^m1J/Ncf1^m1J
B6.Cg-Dock7 +/+ Lepr/J

Genotype: Ncf1^m1J/Ncf1^m1J
involves: C57BL/6

Additional - Ncf1^m1J related