Strain Name:

B6.129X1-Cd2aptm1Shaw/J

Stock Number:

008907

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Homozygous Cd2ap, CD2-associated protein targeted mutant mice die at approximately 6 weeks of age. Cardiac hypertrophy, splenic and thymic atrophy, and ascites may be found upon postmortem examination. Proteinuria can be detected as early as 2 weeks of age, indicating kidney dysfunction. Heterozygotes show increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes.

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; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN15pN1
Generation Definitions
 
Donating InvestigatorDr. Andrey Shaw,   Washington University School of Medicine

Description
Homozygous targeted mutant mice begin to show growth retardation at about 3 weeks of age, and die at approximately 6 weeks. Cardiac hypertrophy, splenic and thymic atrophy, and ascites may be found upon postmortem examination. Proteinuria can be detected as early as 2 weeks of age, indicating kidney dysfunction. The predominant kidney pathology involves glomeruli which become sclerotic by 4 weeks. CD2AP protein is not detected in the thymus, kidney, liver or spleen of homozygous targeted animals. Naive and cultured T cells show increased sensitivity to antigen, increased proliferation, increased number of cell divisions and increased apoptosis compared to wild type cells. Heterozygotes show increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes.

Development
Exon 2, encoding the first SRC homology 3 (SH3) domain, was replaced with a neomycin resistance cassette using 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Mice were backcrossed to C57BL/6 fifteen times by the donating laboratory.

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).
Focal Segmental Glomerulosclerosis 3, Susceptibility To; FSGS3
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.

Cd2aptm1Shaw/Cd2ap+

        Background Not Specified
  • renal/urinary system phenotype
  • abnormal kidney physiology
    • observed immunoglobulin deposits in either punctate or linear patterns at the glomerular basement membrane in 4 out of 20 heterozygotes, however did not develop proteinuria   (MGI Ref ID J:84748)
  • abnormal podocyte morphology
    • ferritin injection did not induce the formation of multivesicular bodies as it did in wildtype   (MGI Ref ID J:84748)
  • abnormal renal glomerulus morphology
    • exhibited glomerular lesions of varying degrees at 9 months of age but not at 6 months of age and this pathology at 9 months of age was similar to that seen in 3-4 week old homozygous null mice   (MGI Ref ID J:84748)
    • observed infiltration of inflammatory leukocytes in some glomeruli   (MGI Ref ID J:84748)
    • observed electon-dense mesangial deposits that occluded the capillary lumen, subepithelial and subendothelial deposits along the glomerular basement membrane, and in some older mice, highly organized microtubular deposits in the mesangium   (MGI Ref ID J:84748)
    • expanded mesangial matrix
      • exhibited expansion of the mesangial matrix at 9 months of age but not at 6 months of age   (MGI Ref ID J:84748)
    • mesangial cell hyperplasia
      • exhibited increased mesangial cellularity at 9 months of age but not at 6 months of age   (MGI Ref ID J:84748)
  • homeostasis/metabolism phenotype
  • increased susceptibility to injury
    • increased susceptibility to glomerular injury when injected with a low dose of nephrotoxic antibody, with heterozygotes developing more severe and persistent proteinuria and even resulting in death of some mutants compared to wildtype   (MGI Ref ID J:84748)

Cd2aptm1Shaw/Cd2aptm1Shaw

        involves: 129X1/SvJ
  • mortality/aging
  • premature death
    • most dead between 6 and 7 weeks of age   (MGI Ref ID J:57971)
  • cardiovascular system phenotype
  • enlarged heart
    • hypertrophy   (MGI Ref ID J:57971)
  • growth/size/body phenotype
  • postnatal growth retardation
    • evident beginning at about 3 weeks of age   (MGI Ref ID J:57971)
  • hematopoietic system phenotype
  • decreased T cell proliferation
    • in response to either concanavalin A (ConA) or CD3   (MGI Ref ID J:57971)
  • spleen atrophy   (MGI Ref ID J:57971)
  • thymus atrophy   (MGI Ref ID J:57971)
  • homeostasis/metabolism phenotype
  • ascites   (MGI Ref ID J:57971)
  • decreased circulating serum albumin level
    • decreased in serum   (MGI Ref ID J:57971)
  • increased blood urea nitrogen level
  • increased circulating creatinine level
    • elevated in blood   (MGI Ref ID J:57971)
  • increased urine protein level   (MGI Ref ID J:57971)
  • immune system phenotype
  • decreased T cell proliferation
    • in response to either concanavalin A (ConA) or CD3   (MGI Ref ID J:57971)
  • spleen atrophy   (MGI Ref ID J:57971)
  • thymus atrophy   (MGI Ref ID J:57971)
  • renal/urinary system phenotype
  • abnormal podocyte morphology
    • loss of integrity between cells, evident at 1 week of age and progressive   (MGI Ref ID J:57971)
  • glomerulosclerosis
    • evident by 4 weeks of age   (MGI Ref ID J:57971)
  • increased urine protein level   (MGI Ref ID J:57971)
  • mesangial cell hyperplasia
    • hyperplasia   (MGI Ref ID J:57971)
  • renal glomerulus hypertrophy
    • increased size and cellularity, porgressivley worse with age   (MGI Ref ID J:57971)
View Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      heart
      kidney
Postnatal Lethality
      Homozygous

Internal/Organ Research
Kidney Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Cd2aptm1Shaw
Allele Name targeted mutation 1, Andrey S Shaw
Allele Type Targeted (knock-out)
Common Name(s) Cd2ap-;
Mutation Made ByDr. Andrey Shaw,   Washington University School of Medicine
Strain of Origin129X1/SvJ
ES Cell Line NameRW-4
ES Cell Line Strain129X1/SvJ
Gene Symbol and Name Cd2ap, CD2-associated protein
Chromosome 17
Gene Common Name(s) AL024079; C78928; CMS; METS-1; Mets1; expressed sequence AL024079; expressed sequence C78928; mesenchyme to epithelium transition protein, SH3 domains;
General Note Heterozygous mutant mice exhibit highly organized microtubular deposits in the mesangium which is characteristic in human immunotactoid glomerulopathy (J:84748).
Molecular Note The sequences encoding the first SRC homology 3 domain was replaced with a neomycin-resistance gene. Immunoblots of kidney, liver, spleen, and thymus proteins from homozygous mice indicated the absence of gene product. [MGI Ref ID J:57971]

Genotyping

Genotyping Information

Genotyping Protocols

Cd2aptm1Shaw, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shih NY; Li J; Karpitskii V; Nguyen A; Dustin ML; Kanagawa O; Miner JH; Shaw AS. 1999. Congenital nephrotic syndrome in mice lacking CD2-associated protein [see comments] Science 286(5438):312-5. [PubMed: 10514378]  [MGI Ref ID J:57971]

Additional References

Cd2aptm1Shaw related

Bredemeyer AJ; Geahlen JH; Weis VG; Huh WJ; Zinselmeyer BH; Srivatsan S; Miller MJ; Shaw AS; Mills JC. 2009. The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage. Dev Biol 325(1):211-24. [PubMed: 19013146]  [MGI Ref ID J:143539]

Grunkemeyer JA; Kwoh C; Huber TB; Shaw AS. 2005. CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP deficiency. J Biol Chem 280(33):29677-81. [PubMed: 15951437]  [MGI Ref ID J:101048]

Huber TB; Kwoh C; Wu H; Asanuma K; Godel M; Hartleben B; Blumer KJ; Miner JH; Mundel P; Shaw AS. 2006. Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J Clin Invest 116(5):1337-45. [PubMed: 16628251]  [MGI Ref ID J:108942]

Jarad G; Cunningham J; Shaw AS; Miner JH. 2006. Proteinuria precedes podocyte abnormalities inLamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest 116(8):2272-9. [PubMed: 16886065]  [MGI Ref ID J:113125]

Kim JM; Wu H; Green G; Winkler CA; Kopp JB; Miner JH; Unanue ER; Shaw AS. 2003. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science 300(5623):1298-300. [PubMed: 12764198]  [MGI Ref ID J:84748]

Lee KH; Dinner AR; Tu C; Campi G; Raychaudhuri S; Varma R; Sims TN; Burack WR; Wu H; Wang J; Kanagawa O; Markiewicz M; Allen PM; Dustin ML; Chakraborty AK; Shaw AS. 2003. The immunological synapse balances T cell receptor signaling and degradation. Science 302(5648):1218-22. [PubMed: 14512504]  [MGI Ref ID J:127901]

Peters I; Tossidou I; Achenbach J; Woroniecki R; Mengel M; Park JK; Paschy M; de Groot K; Haller H; Schiffer M. 2006. IGF-binding protein-3 modulates TGF-beta/BMP-signaling in glomerular podocytes. J Am Soc Nephrol 17(6):1644-56. [PubMed: 16672319]  [MGI Ref ID J:135728]

Russo LM; Srivatsan S; Seaman M; Suleiman H; Shaw AS; Comper WD. 2013. Albuminuria associated with CD2AP knockout mice is primarily due to dysfunction of the renal degradation pathway processing of filtered albumin. FEBS Lett 587(22):3738-41. [PubMed: 24140342]  [MGI Ref ID J:202925]

Schiffer M; Mundel P; Shaw AS; Bottinger EP. 2004. A novel role for the adaptor molecule CD2-associated protein in transforming growth factor-beta-induced apoptosis. J Biol Chem 279(35):37004-12. [PubMed: 15213232]  [MGI Ref ID J:92560]

Schiffer M; Schiffer LE; Gupta A; Shaw AS; Roberts IS; Mundel P; Bottinger EP. 2002. Inhibitory smads and tgf-Beta signaling in glomerular cells. J Am Soc Nephrol 13(11):2657-66. [PubMed: 12397035]  [MGI Ref ID J:103379]

Srivatsan S; Swiecki M; Otero K; Cella M; Shaw AS. 2013. CD2-associated protein regulates plasmacytoid dendritic cell migration, but is dispensable for their development and cytokine production. J Immunol 191(12):5933-40. [PubMed: 24218450]  [MGI Ref ID J:207138]

Tossidou I; Niedenthal R; Klaus M; Teng B; Worthmann K; King BL; Peterson KJ; Haller H; Schiffer M. 2012. CD2AP regulates SUMOylation of CIN85 in podocytes. Mol Cell Biol 32(6):1068-79. [PubMed: 22203040]  [MGI Ref ID J:183631]

Wasik AA; Polianskyte-Prause Z; Dong MQ; Shaw AS; Yates JR 3rd; Farquhar MG; Lehtonen S. 2012. Septin 7 forms a complex with CD2AP and nephrin and regulates glucose transporter trafficking. Mol Biol Cell 23(17):3370-9. [PubMed: 22809625]  [MGI Ref ID J:199675]

Wu F; Saleem MA; Kampik NB; Satchwell TJ; Williamson RC; Blattner SM; Ni L; Toth T; White G; Young MT; Parker MD; Alper SL; Wagner CA; Toye AM. 2010. Anion exchanger 1 interacts with nephrin in podocytes. J Am Soc Nephrol 21(9):1456-67. [PubMed: 20576809]  [MGI Ref ID J:185927]

Xavier S; Niranjan T; Krick S; Zhang T; Ju W; Shaw AS; Schiffer M; Bottinger EP. 2009. TbetaRI independently activates Smad- and CD2AP-dependent pathways in podocytes. J Am Soc Nephrol 20(10):2127-37. [PubMed: 19679673]  [MGI Ref ID J:166322]

Yaddanapudi S; Altintas MM; Kistler AD; Fernandez I; Moller CC; Wei C; Peev V; Flesche JB; Forst AL; Li J; Patrakka J; Xiao Z; Grahammer F; Schiffer M; Lohmuller T; Reinheckel T; Gu C; Huber TB; Ju W; Bitzer M; Rastaldi MP; Ruiz P; Tryggvason K; Shaw AS;Faul C; Sever S; Reiser J. 2011. CD2AP in mouse and human podocytes controls a proteolytic program that regulates cytoskeletal structure and cellular survival. J Clin Invest 121(10):3965-80. [PubMed: 21911934]  [MGI Ref ID J:178223]

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 & HusbandryWhen maintained as a live colony, heterozygotes may be bred. Homozygotes die at 6-7 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* $2450.00
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 11 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* $3185.00
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 11 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.

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