Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Peter J Murray,   St. Jude Children's Research Hospital

Description
These mice possess loxP sites on either side of exons 7 and 8 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 7 and 8 deleted in the cre-expressing tissue(s).

When bred to a strain with inducible Cre recombinase expression in the myeloid cell lineages (see Stock No. 004781, for example ) or endothelial cells (see Stock No. 004128 , for example), this mutant mouse strain may be useful in studies of immune response to bacterial and parasitic infections.

Development
A loxP site flanked targeting vector containing PGK-Neo selection cassette was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 8 of the targeted gene, and another loxP site was inserted upstream of exon 7. This construct was electroporated into C57BL/6 derived Bruce4 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. ES cells that had successfully undergone Cre- mediated recombination and no longer retained the cassette but did retain the loxP-flanked exons 7 and 8 were injected in recipient blastocysts. Resulting chimeric male animals were backcrossed to wildtype C57BL/6 mice. The mice were then backcrossed to BALB/cJ mice for generations before arriving at The Jackson Laboratory.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Arg1^tm1Pmu allele

008817

C57BL/6-Arg1tm1Pmu/J

View Strains carrying   Arg1^tm1Pmu     (1 strain)

Strains carrying other alleles of Arg1

007741	B6.129-Arg1tm1Rki/J
015857	B6.129S4-Arg1tm1Lky/J
015858	C.129S4(B6)-Arg1tm1Lky/J

View Strains carrying other alleles of Arg1     (3 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Argininemia   (ARG1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Arg1^tm1Pmu/Arg1^tm1Pmu Lyz2^tm1(cre)Ifo/?

        B6.Cg-Arg1^tm1Pmu Lyz2^tm1(cre)Ifo   (conditional)

• immune system phenotype
• decreased susceptibility to parasitic infection
  • mice are resistant to the wasting disease caused by systemic infection with T. gondii   (MGI Ref ID J:143229)
  • control mice lose 20% of their body weight by 40 days after T. gondii infection while infected mutant mice have no loss of body weight   (MGI Ref ID J:143229)

Arg1^tm1Pmu/Arg1^tm1Pmu Tg(Tek-cre)1Ywa/?

        B6.Cg-Arg1^tm1Pmu Tg(Tek-cre)1Ywa   (conditional)

• immune system phenotype
• abnormal macrophage physiology
  • very little urea is produced by peritoneal macrophages in response to IL-4 and IL-10 incubation due to a lack of arginase activity   (MGI Ref ID J:143229)
• • increased macrophage nitric oxide production
    • macrophages produce more nitrous oxide in response to LPS stimulation or Mycobacterium bovis infection   (MGI Ref ID J:143229)
• decreased susceptibility to bacterial infection
  • mice infected with M. tuberculosis have lower bacterial counts than wild-type littermates in the lungs after the initial bacterial growth period   (MGI Ref ID J:143229)
  • there is also lower bacterial load in the spleens of the mice 70 days after infection with M. tuberculosis   (MGI Ref ID J:143229)
  • lung granulomas in these infected mice occupy a smaller fraction of the total lung area and have a more pronounced lymphocytic infiltrate   (MGI Ref ID J:143229)
• homeostasis/metabolism phenotype
• abnormal nitric oxide homeostasis
  • there is more NO activity in liver granulomas of mice infected with M. tuberculosis   (MGI Ref ID J:143229)
• • increased macrophage nitric oxide production
    • macrophages produce more nitrous oxide in response to LPS stimulation or Mycobacterium bovis infection   (MGI Ref ID J:143229)

View Research Applications

Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences
Immunology and Inflammation Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Arg1tm1Pmu
Allele Name		targeted mutation 1, Peter J Murray
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Arg1flox;
Mutation Made By		Peter Murray,   St. Jude Children's Research Hospital
Strain of Origin		B6.Cg-Thy1
ES Cell Line Name		Bruce 4
ES Cell Line Strain		B6.Cg-Thy1
Gene Symbol and Name		Arg1, arginase, liver
Chromosome		10
Gene Common Name(s)		AI; AI256583; Arg-1; PGIF; expressed sequence AI256583;
Molecular Note		A loxP site was inserted upstream of exon 7 and a loxP-flanked neomycin selection cassette was inserted downstream of exon 8. Transient expression of cre recombinase removed the neomycin cassette, leaving exons 7 and 8 floxed. These exons encode in addition to the oligomerization domain, two highly conserved aspartic acid residues that are essential to the enzymatic activity of the gene product. Correct targeting was confirmed by genomic PCR. [MGI Ref ID J:143229]

Genotyping

Genotyping Information

Genotyping Protocols

Arg1^tm1Pmu, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

El Kasmi KC; Qualls JE; Pesce JT; Smith AM; Thompson RW; Henao-Tamayo M; Basaraba RJ; Konig T; Schleicher U; Koo MS; Kaplan G; Fitzgerald KA; Tuomanen EI; Orme IM; Kanneganti TD; Bogdan C; Wynn TA; Murray PJ. 2008. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat Immunol 9(12):1399-406. [PubMed: 18978793]  [MGI Ref ID J:143229]

Additional References

Arg1^tm1Pmu related

Schreiber T; Ehlers S; Heitmann L; Rausch A; Mages J; Murray PJ; Lang R; Holscher C. 2009. Autocrine IL-10 induces hallmarks of alternative activation in macrophages and suppresses antituberculosis effector mechanisms without compromising T cell immunity. J Immunol 183(2):1301-12. [PubMed: 19561100]  [MGI Ref ID J:151659]

Stoermer KA; Burrack A; Oko L; Montgomery SA; Borst LB; Gill RG; Morrison TE. 2012. Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus. J Immunol 189(8):4047-59. [PubMed: 22972923]  [MGI Ref ID J:190519]

Wang R; Dillon CP; Shi LZ; Milasta S; Carter R; Finkelstein D; McCormick LL; Fitzgerald P; Chi H; Munger J; Green DR. 2011. The Transcription Factor Myc Controls Metabolic Reprogramming upon T Lymphocyte Activation. Immunity 35(6):871-82. [PubMed: 22195744]  [MGI Ref ID J:179281]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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