Overview

These hepatic arginase (AI)-mutant mice may be useful in studying metabolic defects of arginase I deficiency, urea cycle (excretion of excess nitrogen), and neuronal development and function.

Donating Investigator

Stephen Cederbaum, University of California Los Angeles

Genetic overview

Genetic Background	Generation

Arg1^tm1Rki

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Arg1	arginase, liver

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Research Applications

Research Tools
Metabolism Research
Internal/Organ Research
Developmental Biology Research
Neurobiology Research
Reproductive Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous AI-mutant mice completely lack hepatic arginase (AI) activity, exhibit hyperagrininemia, severe symptoms of hyperammonemia (ncluding decerebrate posture, lethargy, and high-frequency tremor of the extremities, particularly the tail) and die between 10-14 days after birth. Neural stem cells (NCSs) isolated from homozygous mice exhibit abnormal proliferation and differentiation. In addition, haploid germ cells carrying the disrupted AI allele may be less fit/less effective in forming zygotes compared to wild-type spermatozoa. Heterozygotes are viable and fertile. These AI-mutant mice may be useful in studying metabolic defects of arginase I deficiency, urea cycle (excretion of excess nitrogen), and neuronal development and function.

Development

A targeting vector was designed to replace exon 4 of the targeted gene with a neomycin resistance gene. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts, and the resulting chimeric males were bred with C57BL/6 females. Mutant mice were reportedly backcrossed to C57BL/6 mice for ten generations prior to sending to The Jackson Laboratory Repository (see SNP notes below). During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for one generation to establish the colony. After this, mutant mice were bred with wildtype mice from the colony to maintain the strain.

A 32 SNP (single nucleotide polymorphism) panel analysis, with markers covering all 19 chromosomes and the X chromosome, was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed one marker on chromosome 8 and one marker on chromosome 12 that was not fixed for C57BL/6 allele-type (e.g.: still segregating for 129 allele-type markers). The marker on chromosome 8 may be fixed as homozygous for the 129 allele-type. These data suggest the mice may not have been backcrossed to C57BL/6 for as many generations as originally reported prior to arrival at The Jackson Laboratory Repository.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Becker-Catania SG; Gregory TL; Yang Y; Gau CL; de Vellis J; Cederbaum SD; Iyer RK. 2006. Loss of arginase I results in increased proliferation of neural stem cells. J Neurosci Res 84(4):735-46PubMed: 16773651 MGI: J:125486
Iyer RK; Yoo PK; Kern RM; Rozengurt N; Tsoa R; O'Brien WE; Yu H; Grody WW; Cederbaum SD. 2002. Mouse model for human arginase deficiency. Mol Cell Biol 22(13):4491-8PubMed: 12052859 MGI: J:83263

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Genetics

Arg1^tm1Rki

Allele Symbol: Arg1^tm1Rki

Allele Name	targeted mutation 1, Ramaswamy K Iyer
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Arg1^tm1Rki; targeted mutation 1, Ramaswamy K Iyer
Gene Symbol and Name	Arg1, arginase, liver
Gene Synonym(s)	expressed sequence AI256583; AI; Arg-1; AI256583; PGIF; Arg-1
Strain of Origin	Not Specified
Chromosome	10
Molecular Note	A neomycin selection cassette replaced a genomic fragment containing exon 4. Activity assays demonstrated that no functional protein was made from this allele.
Mutations Made By	Ramaswamy Iyer, University of California, Los Angeles

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

hyperargininemia

Research Areas By Genotype

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

Research Tools
- Metabolism Research
- Neurobiology Research
- Developmental Biology Research
- Internal/Organ Research
- Reproductive Biology Research
  - male germ cells
Metabolism Research
- Enzyme Deficiency
Internal/Organ Research
- Liver Defects
Developmental Biology Research
- Internal/Organ Defects
  - liver
- Perinatal Lethality
  - Homozygous
Neurobiology Research
- Tremor Defects
- Metabolic Defects
Reproductive Biology Research
- Fertility Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Arg1^tm1Rki/Arg1^tm1Rki
Not Specified

homeostasis/metabolism phenotype

abnormal circulating amino acid level
- elevated plasma glutamic acid, citrulline and histidine levels: about 1.5 fold greater than the wild-type level
- reduced plasma valine, isoleucine and leucine levels: 0.4 to 0.5 of the level of wild-type

abnormal homeostasis
- total kidney arginase activity levels normal; ARG2 levels are thought to be induced two-fold in these mice

decreased circulating ornithine level
- reduced plasma ornithine levels: one half of the level of wild-type

decreased circulating proline level
- reduced plasma proline levels: one third of the level of wild-type

increased circulating ammonia level
- plasma ammonia levels are increased 10 fold in mice exhibiting metabolic crisis

increased circulating arginine level
- elevated plasma arginine levels: four fold greater than the level of wild-type

increased circulating citrulline level
- elevated plasma citrulline levels

increased circulating histidine level
- elevated plasma histidine levels

liver/biliary system phenotype

abnormal hepatobiliary system morphology

abnormal hepatocyte morphology
- nuclei and cytoplasm enlarged two to three fold in most cells; cytoplasmic inclusions also noted as well as other abnormalities; abnormal nuclei

abnormal liver morphology

enlarged liver

pale liver

mammalian phenotype

nervous system phenotype
- Normal - normal brain morphology; no astrocyte defects noted

mortality/aging

postnatal lethality, complete penetrance
- die at postnatal day 10-14

References

Becker-Catania SG; Gregory TL; Yang Y; Gau CL; de Vellis J; Cederbaum SD; Iyer RK. 2006. Loss of arginase I results in increased proliferation of neural stem cells. J Neurosci Res 84(4):735-46PubMed: 16773651 MGI: J:125486
Iyer RK; Yoo PK; Kern RM; Rozengurt N; Tsoa R; O'Brien WE; Yu H; Grody WW; Cederbaum SD. 2002. Mouse model for human arginase deficiency. Mol Cell Biol 22(13):4491-8PubMed: 12052859 MGI: J:83263

Additional - Arg1^tm1Rki related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Arg1^tm1Rki
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice. Homozygous mice die between 10-14 days after birth.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Arg1^tm1Rki/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007741 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Arg1<tm1Rki>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Arg1tm1Rki

Allele Symbol: Arg1tm1Rki

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Arg1tm1Rki/Arg1tm1RkiNot Specified

homeostasis/metabolism phenotype

liver/biliary system phenotype

mammalian phenotype

mortality/aging

References

Additional - Arg1tm1Rki related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

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

Arg1^tm1Rki

Allele Symbol: Arg1^tm1Rki

Genotype: Arg1^tm1Rki/Arg1^tm1Rki
Not Specified

Additional - Arg1^tm1Rki related