Description

Strain Information

Type Coisogenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   24-SEP-09 Species laboratory mouse Generation N12+N1F8 (18-JUN-12) Generation Definitions   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 C57BL/6 mice for 11 generations before arriving at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Arg1^tm1Pmu allele

008879

C.B6-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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   24-SEP-09
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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 only available to non-profit entities.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

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

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

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 JACKSON, 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 or services by JACKSON.