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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N4+N1   Donating Investigator Maki Wakamiya,   Baylor College of Medicine

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-TgN(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 eosinopilia 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-TgN(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
	Wild-type from the colony
	002448 129S1/SvImJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Ada^tm1Mw allele

003265	FVB;129-Adatm1Mw Tg(PLADA)4118Rkmb/J
003297	FVB;129-Adatm1Mw Tg(PLFSADA)2465Rkmb/J

View Strains carrying   Ada^tm1Mw     (2 strains)

Strains carrying other alleles of Ada

003265

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

View Strains carrying other alleles of Ada     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Priapism, Familial Idiopathic - 5

5 Conditionally targeted allele(s)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ada^tm1Mw/Ada^tm1Mw

        involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

• reproductive system phenotype
• abnormal penile erection function (MGI Ref ID J:135978)
  • mice exhibit increased corpus cavernosal smooth muscle relaxation in response to nerve stimulation
• priapism (MGI Ref ID J:135978)
  • mice exhibit erections lasting up to 72 hours that is associated with increased camp and cGMP production
  • however, treatment with PEG-ADA corrects the observed priapism
  • mice exhibit penile vascular damage, including marked intimal thickening with smooth muscle hypertrophy and endothelial swelling, and fibrosis subsequent to priapism

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

Ada^tm1Mw/Ada^tm1Mw

        involves: 129S7/SvEvBrd * C57BL/6

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:25085)
  • animals die at birth or shortly thereafter
  • only 10% born with beating hearts, but these animals did not move
• growth/size phenotype
• decreased body weight (MGI Ref ID J:25085)
  • 15% smaller than littermates
• homeostasis/metabolism phenotype
• abnormal enzyme/ coenzyme level (MGI Ref ID J:25085)
  • elevated levels of hepatocellular enzymes, aspartate aminotransferase (66%) and alanine aminotransferase (56%)
• abnormal nucleotide metabolism (MGI Ref ID J:25085)
  • dATP levels in fetal blood are elevated 2000-fold while ATP levels are decreased slightly
• cyanosis (MGI Ref ID J:25085)
  • pups born with beating hearts remained cyanotic until death a few hours later
• hypoalbuminemia (MGI Ref ID J:25085)
  • 57% reduction
• hypoproteinemia (MGI Ref ID J:25085)
  • 59% reduction
• immune system phenotype
• decreased T cell number (MGI Ref ID J:25085)
  • decreased numbers of mature T lymphocytes
• liver/biliary system phenotype
• abnormal liver morphology (MGI Ref ID J:25085)
  • livers have disorganized hepatic plates, resulting in isolated packets of cells
• abnormal hepatocyte morphology (MGI Ref ID J:25085)
  • morphological changes in hepatocytes are seen as early as E16.5, including enlarged hepatocytes with karyomegaly, irregularly shaped nuclear envelopes, and a decrease in heterochromatin
  • cytoplasm of hepatocytes has decreased amounts of glycogen and increased volume of rough ER
  • hepatocytes lose their normal polyhedral shape and become round
• decreased hepatocyte number (MGI Ref ID J:25085)
  • decrease in numbers of hepatocytes per lobule
• hepatic necrosis (MGI Ref ID J:25085)
  • evident at E17.5
• small liver (MGI Ref ID J:25085)
  • 29% smaller than littermates
• hematopoietic system phenotype
• decreased T cell number (MGI Ref ID J:25085)
  • decreased numbers of mature T lymphocytes

Ada^tm1Mw/Ada^tm1Mw

        involves: 129S7/SvEvBrd

• immune system phenotype
• abnormal dendritic cell physiology (MGI Ref ID J:138722)
  • lung dendritic cells exhibit increased basal secretion levels of VEGF and CXCL1 and elevated VEGF production in response to NECA compared to in wild-type mice
• increased dendritic cell number (MGI Ref ID J:138722)
  • the number of proangiogenic CD11b^lowCD11c+ dendritic cells in the lungs is increased by 3-fold and they exhibit increased size compared to in wild-type mice
• hematopoietic system phenotype
• increased dendritic cell number (MGI Ref ID J:138722)
  • the number of proangiogenic CD11b^lowCD11c+ dendritic cells in the lungs is increased by 3-fold and they exhibit increased size compared to in wild-type mice

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 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 Origin		129S7/SvEvBrd-Hprt1<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/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]

Genotyping

Genotyping Information

Genotyping Protocols

Ada^tm1Mw, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

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; 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]

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]

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]

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

Colony Maintenance

Breeding & Husbandry	When maintained in a live colony, the strain is maintained by mating heterozygous mutant mice with wildtype siblings.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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
	Wild-type from the colony
	002448 129S1/SvImJ
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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 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 by companies or for-profit entities requires a license prior to shipping.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.