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

Former Names FVB,129-Adatm1Mw-TgN(PLADA)4118Rkmb    (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+7p Generation Definitions   Donating Investigator Dr. Michael R. Blackburn,   Univ Texas Health Science Center

Description
Mice homozygous for the Ada^tm1Mw 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-Ada^tm1Mw 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-Ada^tm1Mw 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   Ada^tm1Mw allele

003297	FVB;129-Adatm1Mw Tg(PLFSADA)2465Rkmb/J
002493	STOCK Adatm1Mw/J

View Strains carrying   Ada^tm1Mw     (2 strains)

Strains carrying other alleles of Ada

003297	FVB;129-Adatm1Mw Tg(PLFSADA)2465Rkmb/J
002346	NOD.NOR-(D2Mit490-Ada)/LtJ
002347	NOR.NOD-(Il1-Ada)/LtJ

View Strains carrying other alleles of Ada     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Negative, Due to Adenosine Deaminase Deficiency

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Ada^tm1Mw/Ada^tm1Mw Tg(PLADA)4118Rkmb/0

        involves: 129S7/SvEvBrd * C57BL/6

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

View Research Applications

Research Applications

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

Ada^tm1Mw related

Developmental Biology Research
Internal/Organ Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
Inflammation
      Asthma

Internal/Organ Research
Liver Defects

Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Adatm1Mw
Allele Name		targeted mutation 1, Maki Wakamiya
Allele Type		Targeted (knock-out)
Common Name(s)		Ada-; adam1;
Mutation Made By		Dr. Maki Wakamiya,   Baylor College of Medicine
Strain of Origin		129S7/SvEvBrd-Hprt<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt<+>
Gene Symbol and Name		Ada, adenosine deaminase
Chromosome		2
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		Dr. Michael Blackburn,   Univ Texas Health Science Center
Expressed Gene		Ada, adenosine deaminase, mouse, laboratory
Promoter		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

Ada^tm1Mw, Standard PCR
Tg(PLADA)4118Rkmb, Tg(PLFSADA)2465Rkmb, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Ada^tm1Mw 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]

Carbonaro DA; Jin X; Wang X; Yu XJ; Rozengurt N; Kaufman ML; Wang X; Gjertson D; Zhou Y; Blackburn MR; Kohn DB. 2012. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction. Blood 120(18):3677-87. [PubMed: 22833548]  [MGI Ref ID J:191331]

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]

Ghaemi Oskouie F; Shameli A; Yang A; Desrosiers MD; Mucsi AD; Blackburn MR; Yang Y; Santamaria P; Shi Y. 2011. High levels of adenosine deaminase on dendritic cells promote autoreactive T cell activation and diabetes in nonobese diabetic mice. J Immunol 186(12):6798-806. [PubMed: 21593382]  [MGI Ref ID J:175471]

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]

Pedroza M; Schneider DJ; Karmouty-Quintana H; Coote J; Shaw S; Corrigan R; Molina JG; Alcorn JL; Galas D; Gelinas R; Blackburn MR. 2011. Interleukin-6 contributes to inflammation and remodeling in a model of adenosine mediated lung injury. PLoS One 6(7):e22667. [PubMed: 21799929]  [MGI Ref ID J:175762]

Sauer AV; Brigida I; Carriglio N; Hernandez RJ; Scaramuzza S; Clavenna D; Sanvito F; Poliani PL; Gagliani N; Carlucci F; Tabucchi A; Roncarolo MG; Traggiai E; Villa A; Aiuti A. 2012. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID. Blood 119(6):1428-39. [PubMed: 22184407]  [MGI Ref ID J:181725]

Sauer AV; Mrak E; Hernandez RJ; Zacchi E; Cavani F; Casiraghi M; Grunebaum E; Roifman CM; Cervi MC; Ambrosi A; Carlucci F; Roncarolo MG; Villa A; Rubinacci A; Aiuti A. 2009. ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. Blood 114(15):3216-26. [PubMed: 19633200]  [MGI Ref ID J:153849]

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]

Wen J; Jiang X; Dai Y; Zhang Y; Tang Y; Sun H; Mi T; Phatarpekar PV; Kellems RE; Blackburn MR; Xia Y. 2010. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling. FASEB J 24(3):740-9. [PubMed: 19858092]  [MGI Ref ID J:158034]

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]

Zhou Y; Mohsenin A; Morschl E; Young HW; Molina JG; Ma W; Sun CX; Martinez-Valdez H; Blackburn MR. 2009. Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor. J Immunol 182(12):8037-46. [PubMed: 19494329]  [MGI Ref ID J:149279]

Tg(PLADA)4118Rkmb related

Carbonaro DA; Jin X; Wang X; Yu XJ; Rozengurt N; Kaufman ML; Wang X; Gjertson D; Zhou Y; Blackburn MR; Kohn DB. 2012. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction. Blood 120(18):3677-87. [PubMed: 22833548]  [MGI Ref ID J:191331]

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]

Sauer AV; Brigida I; Carriglio N; Hernandez RJ; Scaramuzza S; Clavenna D; Sanvito F; Poliani PL; Gagliani N; Carlucci F; Tabucchi A; Roncarolo MG; Traggiai E; Villa A; Aiuti A. 2012. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID. Blood 119(6):1428-39. [PubMed: 22184407]  [MGI Ref ID J:181725]

Sauer AV; Mrak E; Hernandez RJ; Zacchi E; Cavani F; Casiraghi M; Grunebaum E; Roifman CM; Cervi MC; Ambrosi A; Carlucci F; Roncarolo MG; Villa A; Rubinacci A; Aiuti A. 2009. ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. Blood 114(15):3216-26. [PubMed: 19633200]  [MGI Ref ID J:153849]

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

Animal Health Reports

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

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• 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
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.

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