Strain Name:

B6.129S7-Asltm1Brle/J

Stock Number:

018830

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
These Asl (argininosuccinate lyase) conditional hypopmorphic mice are useful in studies of human Argininosuccinic aciduria (ASA), characterized by a persistent intellectual impairment, delayed motor skills and progressive hepatic disease.

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; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating Investigator Brendan Lee,   Baylor College of Medicine

Description
Asl (argininosuccinate lyase) encodes a key enzyme in the urea cycle that catalyzes the breakdown of argininosuccinate to dicarboxylic acid fumarate and the amino acid arginine, a component of the citrulline-nitric oxide (Cit-NO)cycle. Humans with ASL deficiency develop Argininosuccinic aciduria (ASA), characterized by a persistent intellectual impairment, delayed motor skills and progressive hepatic disease.

This targeted mutation strain carries a FRT-flanked neomycin cassette in intron 9 that decreases expression and activity of the gene. These hypomorphic mice are reported to express 15-20% normal levels of protein. Homozygous mice die at 3-4 weeks of age. They show severe postnatal growth retardation, abnormal hair patterning, multiple organ system dysfunction, hyperammonemia, and nitric oxide deficiency. Liver transaminase levels are elevated in plasma, renal creatinine clearance is decreased, and systolic/diastolic blood pressures are elevated compared to wild-type mice. Histological defects are found in multiple organs, involving the immune, hematopoietic, and cardiovascular systems. Heterozygous animals have no phenotype. FLP excision of the neomycin cassette results in phenotypically normal mice.

LoxP sites in introns 6 and 9 make this a conditional allele for generating tissue-specific Cre-generated knockouts. Excision of exons 7-9 stops protein expression.

Development
A loxP site was inserted in intron 6 and an FRT-neomycin-FRT-loxP cassette was introduced to intron 9 using AB2.2 129S7/SvEvBrd-Hprt1+-derived embryonic stem (ES) cells. This strain was backcrossed 5 times to an albino C57BL/6 strain by the donating laboratory (see SNP note below). All animals in the donator's colony are black, suggesting that Tyrc-Brd has been bred out.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Ten markers throughout the genome were segregating for 129, suggesting an incomplete backcross.

Control Information

  Control
   Wild-type male from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- 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).
Argininosuccinic Aciduria
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Asltm1Brle/Asltm1Brle

        involves: 129S7/SvEvBrd
  • mortality/aging
  • premature death
    • mice die within the first 3 to 4 weeks due to multiorgan failure   (MGI Ref ID J:180208)
    • however, mice treated with sodium nitrite, arginine, arginine and sodium benzoate, or all three therapies exhibit improved survival   (MGI Ref ID J:180208)
  • immune system phenotype
  • decreased lymphocyte cell number
    • in the spleen and thymus   (MGI Ref ID J:180208)
  • decreased spleen germinal center number   (MGI Ref ID J:180208)
  • increased macrophage cell number
    • in the thymus cortex   (MGI Ref ID J:180208)
  • increased spleen red pulp amount   (MGI Ref ID J:180208)
  • thymus cortex hypoplasia
  • homeostasis/metabolism phenotype
  • abnormal circulating amino acid level
    • mice exhibit increased plasma citrulline and decreased arginine levels compared with wild-type mice   (MGI Ref ID J:180208)
  • abnormal nitric oxide homeostasis
    • decreased nitrosylation in the liver and heart   (MGI Ref ID J:180208)
  • decreased circulating alanine transaminase level   (MGI Ref ID J:180208)
  • decreased circulating aspartate transaminase level   (MGI Ref ID J:180208)
  • increased circulating ammonia level   (MGI Ref ID J:180208)
  • cardiovascular system phenotype
  • abnormal myocardial fiber morphology
    • atrophic in the myocardium   (MGI Ref ID J:180208)
  • decreased vasodilation
    • impaired in response to acetylcholine treatment   (MGI Ref ID J:180208)
    • however, relaxation in response to sodium nitroprusside is normal   (MGI Ref ID J:180208)
  • increased systemic arterial diastolic blood pressure
    • however, mice treated with sodium nitrite, arginine and sodium benzoate exhibit normalizes blood pressure   (MGI Ref ID J:180208)
  • increased systemic arterial systolic blood pressure
    • however, mice treated with sodium nitrite, arginine and sodium benzoate exhibit normalizes blood pressure   (MGI Ref ID J:180208)
  • integument phenotype
  • abnormal coat/ hair morphology
    • abnormal hair patterning by 2 weeks of age   (MGI Ref ID J:180208)
  • abnormal dermal layer morphology
  • abnormal hair follicle morphology
    • small and disorganized   (MGI Ref ID J:180208)
    • small hair follicles   (MGI Ref ID J:180208)
  • epidermal atrophy   (MGI Ref ID J:180208)
  • growth/size/body phenotype
  • decreased body weight
    • at 3 and 4 weeks of age   (MGI Ref ID J:180208)
    • however, mice treated with sodium nitrite or sodium nitrite, arginine and sodium benzoate exhibit increased weight   (MGI Ref ID J:180208)
  • postnatal growth retardation
    • by 2 weeks of age   (MGI Ref ID J:180208)
  • renal/urinary system phenotype
  • abnormal renal glomerulus morphology
    • smaller than in wild-type mice   (MGI Ref ID J:180208)
  • decreased creatinine clearance   (MGI Ref ID J:180208)
  • muscle phenotype
  • abnormal myocardial fiber morphology
    • atrophic in the myocardium   (MGI Ref ID J:180208)
  • decreased vasodilation
    • impaired in response to acetylcholine treatment   (MGI Ref ID J:180208)
    • however, relaxation in response to sodium nitroprusside is normal   (MGI Ref ID J:180208)
  • hematopoietic system phenotype
  • abnormal erythrocyte morphology
    • mice exhibit more numerous acanthocytes and fewer spherocytes than in wild-type mice   (MGI Ref ID J:180208)
    • acanthocytosis
      • more numerous acanthocytes than in wild-type mice   (MGI Ref ID J:180208)
  • decreased lymphocyte cell number
    • in the spleen and thymus   (MGI Ref ID J:180208)
  • decreased spleen germinal center number   (MGI Ref ID J:180208)
  • increased macrophage cell number
    • in the thymus cortex   (MGI Ref ID J:180208)
  • increased spleen red pulp amount   (MGI Ref ID J:180208)
  • thymus cortex hypoplasia
  • endocrine/exocrine gland phenotype
  • thymus cortex hypoplasia
View Research Applications

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

Cardiovascular Research
Heart Abnormalities

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)
Postnatal Lethality
      Homozygous

Immunology, Inflammation and Autoimmunity Research

Internal/Organ Research
Heart Abnormalities
Kidney Defects
Liver Defects
Lymphoid Tissue Defects
Spleen Defects

Research Tools
Cre-lox System
      loxP-flanked Sequences
FLP-FRT System
      FRT-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Asltm1Brle
Allele Name targeted mutation 1, Brendan Lee
Allele Type Targeted (Conditional ready (e.g. floxed), Hypomorph)
Common Name(s) AslNeo;
Mutation Made By Brendan Lee,   Baylor College of Medicine
Strain of Origin129S7/SvEvBrd-Hprt
Gene Symbol and Name Asl, argininosuccinate lyase
Chromosome 5
Gene Common Name(s) 2510006M18Rik; ASAL; RIKEN cDNA 2510006M18 gene;
Molecular Note A loxP site was inserted downstream of exon 7. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 9. Western blot analysis confirmed a reduction in protein expression. This allele is hypomorphic. [MGI Ref ID J:180208]

Genotyping

Genotyping Information

Genotyping Protocols

Asltm1Brle,

Separated MCA


Asltm1Brle, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Asltm1Brle related

Erez A; Nagamani SC; Shchelochkov OA; Premkumar MH; Campeau PM; Chen Y; Garg HK; Li L; Mian A; Bertin TK; Black JO; Zeng H; Tang Y; Reddy AK; Summar M; O'Brien WE; Harrison DG; Mitch WE; Marini JC; Aschner JL; Bryan NS; Lee B. 2011. Requirement of argininosuccinate lyase for systemic nitric oxide production. Nat Med 17(12):1619-26. [PubMed: 22081021]  [MGI Ref ID J:180208]

Nagamani SC; Campeau PM; Shchelochkov OA; Premkumar MH; Guse K; Brunetti-Pierri N; Chen Y; Sun Q; Tang Y; Palmer D; Reddy AK; Li L; Slesnick TC; Feig DI; Caudle S; Harrison D; Salviati L; Marini JC; Bryan NS; Erez A; Lee B. 2012. Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria. Am J Hum Genet 90(5):836-46. [PubMed: 22541557]  [MGI Ref ID J:196817]

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 & HusbandryHeterozygotes are viable and fertile. Homozygotes die at 3-4 weeks of age.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type male from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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