Strain Name:

FVB;129-Adatm1Mw Tg(PLADA)4118Rkmb/J

Stock Number:

003265

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Terms of Use

Description

Strain Information

Former Names FVB,129-Adatm1Mw-TgN(PLADA)4118Rkmb    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation; Transgenic;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
GenerationF?+7p
 
Donating Investigator Michael Blackburn,   Univ Texas Health Science Center

Description
Mice homozygous for the Adatm1Mw targeted mutation die perinatally. They show defects in purine metabolism and have liver cell degeneration. Death is most likely the result of accumulation of ADA precursors. Mice from the double mutant strain FVB,129-Adatm1Mw Tg(PLADA)4118Rkmb/J (Stock No. 003265) are rescued from embryonic lethality by transgenic ADA expression in the placenta. Rescued mice that are homozygous for the null Ada allele exhibit a severe combined immunodeficiency. In addition, mice develop a severe lung eosinophilia reminescent of that seen in humans with asthma. Abnormalities were also found in the bone and kidney. ADA deficient mice die from severe respiratory distress by three weeks of age. Mice carrying a transgene overexpressiong ADA in both the placenta and forestomach, FVB;129-Adatm1Mw Tg(PLFSADA)2465Rkmb/J (Stock No. 003297), are rescued from postnatal lethality at three weeks of age. Rescued mice that are homozygous for the null Ada allele live a normal lifespan displaying only a partial immune deficiency and developing less severe pulmonary inflammation.

Control Information

  Control
   Noncarrier
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Adatm1Mw allele
003297   FVB;129-Adatm1Mw Tg(PLFSADA)2465Rkmb/J
002493   STOCK Adatm1Mw/J
View Strains carrying   Adatm1Mw     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms
Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Negative, Due to Adenosine Deaminase Deficiency - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Adatm1Mw/Adatm1Mw Tg(PLADA)4118Rkmb/0

        involves: 129S7/SvEvBrd * C57BL/6
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID J:73418)
    • death by 3 weeks of age
  • hematopoietic system phenotype
  • abnormal spleen red pulp morphology (MGI Ref ID J:73418)
    • with decreased numbers of red blood cells and few megakaryocytes observed
  • abnormal thymus cellularity (MGI Ref ID J:73418)
    • with substantially reduced lymphoid cell counts
  • abnormal thymus lobule morphology (MGI Ref ID J:73418)
    • with decreased cortical-medullary demarcation
  • anemia (MGI Ref ID J:73418)
  • decreased leukocyte cell number (MGI Ref ID J:73418)
    • decreased double-positive T cell number (MGI Ref ID J:73418)
      • in both thymus and spleen
  • increased double-negative T cell number (MGI Ref ID J:73418)
    • in thymus
  • increased granulocyte number (MGI Ref ID J:73418)
    • increased eosinophil cell number (MGI Ref ID J:73418)
  • increased macrophage cell number (MGI Ref ID J:73418)
  • small spleen (MGI Ref ID J:73418)
    • spleen hypoplasia (MGI Ref ID J:73418)
      • lymphoid counts substantially reduced
  • small thymus (MGI Ref ID J:73418)
  • immune system phenotype
  • abnormal spleen red pulp morphology (MGI Ref ID J:73418)
    • with decreased numbers of red blood cells and few megakaryocytes observed
  • abnormal thymus cellularity (MGI Ref ID J:73418)
    • with substantially reduced lymphoid cell counts
  • abnormal thymus lobule morphology (MGI Ref ID J:73418)
    • with decreased cortical-medullary demarcation
  • decreased immunoglobulin level (MGI Ref ID J:73418)
  • decreased leukocyte cell number (MGI Ref ID J:73418)
    • decreased double-positive T cell number (MGI Ref ID J:73418)
      • in both thymus and spleen
  • increased double-negative T cell number (MGI Ref ID J:73418)
    • in thymus
  • increased granulocyte number (MGI Ref ID J:73418)
    • increased eosinophil cell number (MGI Ref ID J:73418)
  • increased macrophage cell number (MGI Ref ID J:73418)
  • lung inflammation (MGI Ref ID J:73418)
    • evidence of inflammatory cells, thickening and shedding of airway epithelium and occlusion of airways with mucous and cellular debris
  • small spleen (MGI Ref ID J:73418)
    • spleen hypoplasia (MGI Ref ID J:73418)
      • lymphoid counts substantially reduced
  • small thymus (MGI Ref ID J:73418)
  • renal/urinary system phenotype
  • abnormal renal glomerulus morphology (MGI Ref ID J:73418)
    • increased red blood cells within glomeruli
  • abnormal renal tubule morphology (MGI Ref ID J:73418)
    • increased red blood cells within convoluted tubules
  • respiratory system phenotype
  • lung inflammation (MGI Ref ID J:73418)
    • evidence of inflammatory cells, thickening and shedding of airway epithelium and occlusion of airways with mucous and cellular debris
  • tachypnea (MGI Ref ID J:73418)
    • evident beginning at postnatal day 12 and progressively labored breathing until death
  • skeleton phenotype
  • abnormal rib morphology (MGI Ref ID J:73418)
    • enlarged costochondral junctions
    • severe rib curvature
View Research Applications

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

Adatm1Mw related

Developmental Biology Research
Internal/Organ Defects

Immunology and Inflammation Research
Immunodeficiency
Inflammation (Asthma)

Internal/Organ Research
Liver Defects

Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol Adatm1Mw
Allele Name targeted mutation 1, Maki Wakamiya
Allele Type Targeted (knock-out)
Common Name(s) Ada-; adam1;
Mutation Made By Maki Wakamiya,   Baylor College of Medicine
Strain of Origin129S7/SvEvBrd-Hprt1<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name Ada, adenosine deaminase
Chromosome 2
Gene Common Name(s) MGC108610;
Molecular Note A neomycin selection cassette was inserted into exon 5. Activity assays demonstrated that no functional protein was made from this allele in homozygous mice. [MGI Ref ID J:25085]
 
Allele Symbol Tg(PLADA)4118Rkmb
Allele Name transgene insertion 4118, Michael R Blackburn
Allele Type Transgenic (random, expressed)
Mutation Made By Michael Blackburn,   Univ Texas Health Science Center
Expressed Gene Ada, adenosine deaminase, mouse, laboratory
Molecular Note A construct was made that contained the endogenous polyadenylation sequence, intron 11, and ~2kb of of the 3' flanking region of the gene. The endogenous promoter was replaced with a promoter containing a 36-bp deletion in the 5'-untranslated region and770-bp trophoblast regulatory element. This resulted in a construct that allowed expression in the placenta prenatally only, while the 36-bp deletion in the promoter allowed distinction of this transcript from that of native transcript. Enzymatic activity of the protein product was not detected in any of the tissues tested at postnatal day 17 in transgenic mice. [MGI Ref ID J:73418]

Genotyping

Genotyping Information

Genotyping Protocols

Adatm1Mw, STD PCR, vers. 1
Tg(PLADA)4118Rkmb, Tg(PLFSADA)2465Rkmb, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Blackburn MR; Datta SK; Kellems RE. 1998. Adenosine deaminase-deficient mice generated using a two-stage genetic engineering strategy exhibit a combined immunodeficiency. J Biol Chem 273(9):5093-100. [PubMed: 9478961]  [MGI Ref ID J:73418]

Additional References

Shi D; Winston JH; Blackburn MR; Datta SK; Hanten G; Kellems RE. 1997. Diverse genetic regulatory motifs required for murine adenosine deaminase gene expression in the placenta. J Biol Chem 272(4):2334-41. [PubMed: 8999942]  [MGI Ref ID J:38454]

Wakamiya M; Blackburn MR; Jurecic R; McArthur MJ; Geske RS; Cartwright J Jr; Mitani K; Vaishnav S; Belmont JW; Kellems RE; Finegold MJ; Montgomery Jr CA; Bradley A; Caskey CT.. 1995. Disruption of the adenosine deaminase gene causes hepatocellular impairment and perinatal lethality in mice. Proc Natl Acad Sci U S A 92(9):3673-7. [PubMed: 7731963]  [MGI Ref ID J:25085]

Adatm1Mw related

Aldrich MB; Chen W; Blackburn MR; Martinez-Valdez H; Datta SK; Kellems RE. 2003. Impaired germinal center maturation in adenosine deaminase deficiency. J Immunol 171(10):5562-70. [PubMed: 14607964]  [MGI Ref ID J:106733]

Apasov S; Chen JF; Smith P; Sitkovsky M. 2000. A(2A) receptor dependent and A(2A) receptor independent effects of extracellular adenosine on murine thymocytes in conditions of adenosine deaminase deficiency Blood 95(12):3859-67. [PubMed: 10845921]  [MGI Ref ID J:63086]

Apasov SG; Blackburn MR; Kellems RE; Smith PT; Sitkovsky MV. 2001. Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling. J Clin Invest 108(1):131-41. [PubMed: 11435465]  [MGI Ref ID J:110739]

Banerjee SK; Young HW; Barczak A; Erle DJ; Blackburn MR. 2004. Abnormal alveolar development associated with elevated adenine nucleosides. Am J Respir Cell Mol Biol 30(1):38-50. [PubMed: 12855405]  [MGI Ref ID J:95133]

Blackburn MR; Datta SK; Wakamiya M; Vartabedian BS; Kellems RE. 1996. Metabolic and immunologic consequences of limited adenosine deaminase expression in mice. J Biol Chem 271(25):15203-10. [PubMed: 8663040]  [MGI Ref ID J:96688]

Blackburn MR; Knudsen TB; Kellems RE. 1997. Genetically engineered mice demonstrate that adenosine deaminase is essential for early postimplantation development. Development 124(16):3089-97. [PubMed: 9272950]  [MGI Ref ID J:42444]

Blackburn MR; Volmer JB; Thrasher JL; Zhong H; Crosby JR; Lee JJ; Kellems RE. 2000. Metabolic consequences of adenosine deaminase deficiency in mice are associated with defects in alveogenesis, pulmonary inflammation, and airway obstruction J Exp Med 192(2):159-70. [PubMed: 10899903]  [MGI Ref ID J:63493]

Blackburn MR; Wakamiya M; Caskey CT; Kellems RE. 1995. Tissue-specific rescue suggests that placental adenosine deaminase is important for fetal development in mice. J Biol Chem 270(41):23891-4. [PubMed: 7592575]  [MGI Ref ID J:29350]

Chunn JL; Mohsenin A; Young HW; Lee CG; Elias JA; Kellems RE; Blackburn MR. 2006. Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations. Am J Physiol Lung Cell Mol Physiol 290(3):L579-87. [PubMed: 16258000]  [MGI Ref ID J:107355]

Chunn JL; Molina JG; Mi T; Xia Y; Kellems RE; Blackburn MR. 2005. Adenosine-dependent pulmonary fibrosis in adenosine deaminase-deficient mice. J Immunol 175(3):1937-46. [PubMed: 16034138]  [MGI Ref ID J:107266]

Chunn JL; Young HW; Banerjee SK; Colasurdo GN; Blackburn MR. 2001. Adenosine-dependent airway inflammation and hyperresponsiveness in partially adenosine deaminase-deficient mice. J Immunol 167(8):4676-85. [PubMed: 11591798]  [MGI Ref ID J:72057]

Fernandez P; Trzaska S; Wilder T; Chiriboga L; Blackburn MR; Cronstein BN; Chan ES. 2008. Pharmacological blockade of A2A receptors prevents dermal fibrosis in a model of elevated tissue adenosine. Am J Pathol 172(6):1675-82. [PubMed: 18467695]  [MGI Ref ID J:136216]

Mi T; Abbasi S; Zhang H; Uray K; Chunn JL; Xia LW; Molina JG; Weisbrodt NW; Kellems RE; Blackburn MR; Xia Y. 2008. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling. J Clin Invest 118(4):1491-501. [PubMed: 18340377]  [MGI Ref ID J:135978]

Mohsenin A; Burdick MD; Molina JG; Keane MP; Blackburn MR. 2007. Enhanced CXCL1 production and angiogenesis in adenosine-mediated lung disease. FASEB J 21(4):1026-36. [PubMed: 17227950]  [MGI Ref ID J:134751]

Mohsenin A; Mi T; Xia Y; Kellems RE; Chen JF; Blackburn MR. 2007. Genetic removal of the A2A adenosine receptor enhances pulmonary inflammation, mucin production, and angiogenesis in adenosine deaminase-deficient mice. Am J Physiol Lung Cell Mol Physiol 293(3):L753-61. [PubMed: 17601796]  [MGI Ref ID J:128038]

Novitskiy SV; Ryzhov S; Zaynagetdinov R; Goldstein AE; Huang Y; Tikhomirov OY; Blackburn MR; Biaggioni I; Carbone DP; Feoktistov I; Dikov MM. 2008. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 112(5):1822-31. [PubMed: 18559975]  [MGI Ref ID J:138722]

Sun CX; Young HW; Molina JG; Volmer JB; Schnermann J; Blackburn MR. 2005. A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. J Clin Invest 115(1):35-43. [PubMed: 15630442]  [MGI Ref ID J:95142]

Sun CX; Zhong H; Mohsenin A; Morschl E; Chunn JL; Molina JG; Belardinelli L; Zeng D; Blackburn MR. 2006. Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury. J Clin Invest 116(8):2173-2182. [PubMed: 16841096]  [MGI Ref ID J:113120]

Turner CP; Seli M; Ment L; Stewart W; Yan H; Johansson B; Fredholm BB; Blackburn M; Rivkees SA. 2003. A1 adenosine receptors mediate hypoxia-induced ventriculomegaly. Proc Natl Acad Sci U S A 100(20):11718-22. [PubMed: 12975523]  [MGI Ref ID J:85820]

Van De Wiele CJ; Joachims ML; Fesler AM; Vaughn JG; Blackburn MR; McGee ST; Thompson LF. 2006. Further differentiation of murine double-positive thymocytes is inhibited in adenosine deaminase-deficient murine fetal thymic organ culture. J Immunol 176(10):5925-33. [PubMed: 16670300]  [MGI Ref ID J:131709]

Wakamiya M; Blackburn MR; Jurecic R; McArthur MJ; Geske RS; Cartwright J Jr; Mitani K; Vaishnav S; Belmont JW; Kellems RE; Finegold MJ; Montgomery Jr CA; Bradley A; Caskey CT.. 1995. Disruption of the adenosine deaminase gene causes hepatocellular impairment and perinatal lethality in mice. Proc Natl Acad Sci U S A 92(9):3673-7. [PubMed: 7731963]  [MGI Ref ID J:25085]

Willems L; Reichelt ME; Molina JG; Sun CX; Chunn JL; Ashton KJ; Schnermann J; Blackburn MR; Headrick JP. 2006. Effects of adenosine deaminase and A1 receptor deficiency in normoxic and ischaemic mouse hearts. Cardiovasc Res 71(1):79-87. [PubMed: 16626672]  [MGI Ref ID J:111146]

Xu PA; Kellems RE. 2000. Function of murine adenosine deaminase in the gastrointestinal tract. Biochem Biophys Res Commun 269(3):749-57. [PubMed: 10720488]  [MGI Ref ID J:110603]

Young HW; Molina JG; Dimina D; Zhong H; Jacobson M; Chan LN; Chan TS; Lee JJ; Blackburn MR. 2004. A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice. J Immunol 173(2):1380-9. [PubMed: 15240734]  [MGI Ref ID J:91943]

Zhong H; Chunn JL; Volmer JB; Fozard JR; Blackburn MR. 2001. Adenosine-mediated mast cell degranulation in adenosine deaminase-deficient mice. J Pharmacol Exp Ther 298(2):433-40. [PubMed: 11454903]  [MGI Ref ID J:132588]

Tg(PLADA)4118Rkmb related

Chunn JL; Mohsenin A; Young HW; Lee CG; Elias JA; Kellems RE; Blackburn MR. 2006. Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations. Am J Physiol Lung Cell Mol Physiol 290(3):L579-87. [PubMed: 16258000]  [MGI Ref ID J:107355]

Turner CP; Seli M; Ment L; Stewart W; Yan H; Johansson B; Fredholm BB; Blackburn M; Rivkees SA. 2003. A1 adenosine receptors mediate hypoxia-induced ventriculomegaly. Proc Natl Acad Sci U S A 100(20):11718-22. [PubMed: 12975523]  [MGI Ref ID J:85820]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Control
   Noncarrier
   Wild-type from the colony
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions


See Terms of Use


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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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
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General inquiries

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

JAX® Mice & Services Conditions of Use

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