Strain Name:

STOCK Inpp5dtm1Dmt/J

Stock Number:

003534

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Availability:

Cryopreserved - Ready for recovery

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.
Specieslaboratory mouse
 
Donating InvestigatorDr. Dan Dumont,   Sunnybrook Health Center

Appearance
white-bellied agouti
Related Genotype: Aw/?

black
Related Genotype: a/a

Description
Inpp5d (commonly called SHIP) -deficient mice are viable and fertile. However, fertility rate is 10% lower in homozygotes and lifespan is shortened in comparison to controls. Inpp5d -deficient mice exhibit dramatic chronic hyperplasia of myeloid cells resulting in splenomegaly, lymphadenopathy and myeloid infiltration of vital organs. Histological and flow studies demonstrate a substantial increase in granulocyte-macrophage/monocyte populations in bone marrow, spleen and lymph nodes. Spleens and lymph nodes are severely enlarged compared to wildtype. The difference in spleen size is apparent as early as 4 weeks of age, and by 16 weeks of age, spleens from null mice are 10 fold greater than those of wildtype mice. Neutrophils and bone marrow-derived mast cells from these mice appear to be less susceptible to apoptotic stimuli.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Inpp5d
024808   B6.Cg-Tg(Inpp5d-EGFP)DLrr/CprJ
View Strains carrying other alleles of Inpp5d     (1 strain)

Phenotype

Phenotype Information

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.

Inpp5dtm1Dmt/Inpp5dtm1Dmt

        involves: 129P2/OlaHsd
  • mortality/aging
  • premature death
    • short life span   (MGI Ref ID J:77739)
  • immune system phenotype
  • abnormal leukocyte physiology
    • myeloid cells exhibit decreased susceptibility to apoptosis induced by sorbitol, cycloheximide, anisomycin and Fas stimulation compared to wild-type cells   (MGI Ref ID J:77739)
  • decreased B cell number
    • B220+CD19+sIgM+ B cells are decreased in the bone marrow, and sIgD+sIgM+ B cells are decreased in the secondary lymphatic organs compared to in wild-type mice   (MGI Ref ID J:77739)
  • enlarged lymph nodes   (MGI Ref ID J:77739)
  • enlarged spleen
    • 4-fold at 6 to 8 weeks, 8-fold at 10 weeks, and greater than 10-fold at 16 weeks   (MGI Ref ID J:77739)
  • increased leukocyte cell number
    • the granulocyte-macrophage/monocyte populations are increased in the spleen compared to in wild-type mice   (MGI Ref ID J:77739)
    • mice exhibit an infiltration of monocyte/macrophage and granulocyte cells in the thymus, lymph nodes, liver, kidney, heart, skeletal muscle, connective tissue, exocrine pancreas, and lungs unlike in wild-type mice   (MGI Ref ID J:77739)
  • hematopoietic system phenotype
  • abnormal leukocyte physiology
    • myeloid cells exhibit decreased susceptibility to apoptosis induced by sorbitol, cycloheximide, anisomycin and Fas stimulation compared to wild-type cells   (MGI Ref ID J:77739)
  • decreased B cell number
    • B220+CD19+sIgM+ B cells are decreased in the bone marrow, and sIgD+sIgM+ B cells are decreased in the secondary lymphatic organs compared to in wild-type mice   (MGI Ref ID J:77739)
  • enlarged spleen
    • 4-fold at 6 to 8 weeks, 8-fold at 10 weeks, and greater than 10-fold at 16 weeks   (MGI Ref ID J:77739)
  • increased leukocyte cell number
    • the granulocyte-macrophage/monocyte populations are increased in the spleen compared to in wild-type mice   (MGI Ref ID J:77739)
    • mice exhibit an infiltration of monocyte/macrophage and granulocyte cells in the thymus, lymph nodes, liver, kidney, heart, skeletal muscle, connective tissue, exocrine pancreas, and lungs unlike in wild-type mice   (MGI Ref ID J:77739)

Inpp5dtm1Dmt/Inpp5dtm1Dmt

        involves: 129P2/OlaHsd * C57BL/6
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation
    • induced thrombi are smaller, contain fewer platelets, and exhibit decreased close cell-cell contact compared to in wild-type mice   (MGI Ref ID J:121283)
    • when exposed to thrombin and atroxin, platelets fail to exhibit induced fibrin clot retraction as do wild-type cells   (MGI Ref ID J:121283)
    • however, mice are not protected against thromboembolism   (MGI Ref ID J:121283)
    • abnormal platelet activation
      • under thrombin stimulation, platelets fail to undergo normal degranulation and form fewer membrane extensions than wild-type cells   (MGI Ref ID J:121283)
      • decreased platelet aggregation
        • in vitro or under flow, platelet aggregation in response to thrombin, collagen, or thomboxane A2 is decreased compared to controls; platelet aggregates that do form are smaller   (MGI Ref ID J:121283)
    • increased bleeding time   (MGI Ref ID J:121283)
  • hematopoietic system phenotype
  • abnormal platelet activation
    • under thrombin stimulation, platelets fail to undergo normal degranulation and form fewer membrane extensions than wild-type cells   (MGI Ref ID J:121283)
    • decreased platelet aggregation
      • in vitro or under flow, platelet aggregation in response to thrombin, collagen, or thomboxane A2 is decreased compared to controls; platelet aggregates that do form are smaller   (MGI Ref ID J:121283)

Inpp5dtm1Dmt/Inpp5dtm1Dmt

        B6.129P2/OlaHsd-Inpp5dtm1Dmt
  • mortality/aging
  • premature death
    • 50% survival at 6 months of age   (MGI Ref ID J:173266)
  • respiratory system phenotype
  • abnormal pulmonary alveolus morphology
    • alveoli of 6 month mice are filled with lipid laden macrophage containing eosinophilic Ym1 crystals   (MGI Ref ID J:173266)
  • respiratory failure
    • in 50% of mice at 6 months of age   (MGI Ref ID J:173266)
  • hematopoietic system phenotype
  • anemia
    • in 4 week old mice   (MGI Ref ID J:173266)
  • decreased lymphocyte cell number
    • reduced mature B cells in bone marrow at 10 weeks of age   (MGI Ref ID J:173266)
    • decreased pre-B cell number
      • reduced pre-B cells in bone marrow at 10 weeks of age   (MGI Ref ID J:173266)
  • decreased platelet cell number
    • in 4 week old mice   (MGI Ref ID J:173266)
  • immune system phenotype
  • decreased lymphocyte cell number
    • reduced mature B cells in bone marrow at 10 weeks of age   (MGI Ref ID J:173266)
    • decreased pre-B cell number
      • reduced pre-B cells in bone marrow at 10 weeks of age   (MGI Ref ID J:173266)
  • increased circulating interleukin-6 level
    • circulating levels elevated   (MGI Ref ID J:173266)
    • levels in bone marrow macrophage are normal but elevated in peritoneal and splenic macrophage   (MGI Ref ID J:173266)
  • homeostasis/metabolism phenotype
  • increased circulating interleukin-6 level
    • circulating levels elevated   (MGI Ref ID J:173266)
    • levels in bone marrow macrophage are normal but elevated in peritoneal and splenic macrophage   (MGI Ref ID J:173266)
View Research Applications

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

Inpp5dtm1Dmt related

Cancer Research
Genes Regulating Growth and Proliferation

Cell Biology Research
Genes Regulating Growth and Proliferation

Hematological Research
Hematopoietic Defects

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules
Lymphoid Tissue Defects
      myeloid hyperplasia

Internal/Organ Research
Lymphoid Tissue Defects
Spleen Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Inpp5dtm1Dmt
Allele Name targeted mutation 1, Dan Dumont
Allele Type Targeted (Null/Knockout)
Common Name(s) SHIP-1-; SHIP1-; Ship -;
Mutation Made ByDr. Dan Dumont,   Sunnybrook Health Center
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Inpp5d, inositol polyphosphate-5-phosphatase D
Chromosome 1
Gene Common Name(s) AI323613; SHIP; SHIP-1; SHIP1; SIP-145; Src homology 2 domain-containing inositol-5-phosphatase; expressed sequence AI323613; hp51CN; p150Ship; s-SHIP;
Molecular Note A neomycin resistance cassette replaced all of exon 1 and part of intron 1. [MGI Ref ID J:72477]

Genotyping

Genotyping Information

Genotyping Protocols

Generic LacZ, Standard PCR
Generic Neo Melt Curve Analysis,

MELT


Inpp5dtm1Dmt-Alternate 3, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Liu Q; Sasaki T; Kozieradzki I; Wakeham A; Itie A; Dumont DJ; Penninger JM. 1999. SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt activation and myeloid cell survival. Genes Dev 13(7):786-91. [PubMed: 10197978]  [MGI Ref ID J:77739]

Additional References

Inpp5dtm1Dmt related

Chari R; Kim S; Murugappan S; Sanjay A; Daniel JL; Kunapuli SP. 2009. Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule secretion. Blood 114(14):3056-63. [PubMed: 19587372]  [MGI Ref ID J:153266]

Duan M; Li WC; Vlahos R; Maxwell MJ; Anderson GP; Hibbs ML. 2012. Distinct macrophage subpopulations characterize acute infection and chronic inflammatory lung disease. J Immunol 189(2):946-55. [PubMed: 22689883]  [MGI Ref ID J:189549]

Harder KW; Quilici C; Naik E; Inglese M; Kountouri N; Turner A; Zlatic K; Tarlinton DM; Hibbs ML. 2004. Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1. Blood 104(13):3901-10. [PubMed: 15339845]  [MGI Ref ID J:95291]

Horan KA; Watanabe K; Kong AM; Bailey CG; Rasko JE; Sasaki T; Mitchell CA. 2007. Regulation of FcgammaR-stimulated phagocytosis by the 72-kDa inositol polyphosphate 5-phosphatase: SHIP1, but not the 72-kDa 5-phosphatase, regulates complement receptor 3 mediated phagocytosis by differential recruitment of these 5-phosphatases to the phagocytic cup. Blood 110(13):4480-91. [PubMed: 17682126]  [MGI Ref ID J:149114]

Krebs DL; Chehal MK; Sio A; Huntington ND; Da ML; Ziltener P; Inglese M; Kountouri N; Priatel JJ; Jones J; Tarlinton DM; Anderson GP; Hibbs ML; Harder KW. 2012. Lyn-dependent signaling regulates the innate immune response by controlling dendritic cell activation of NK cells. J Immunol 188(10):5094-105. [PubMed: 22491248]  [MGI Ref ID J:188683]

Lakhanpal GK; Vecchiarelli-Federico LM; Li YJ; Cui JW; Bailey ML; Spaner DE; Dumont DJ; Barber DL; Ben-David Y. 2010. The inositol phosphatase SHIP-1 is negatively regulated by Fli-1 and its loss accelerates leukemogenesis. Blood 116(3):428-36. [PubMed: 20445019]  [MGI Ref ID J:162792]

Liang OD; Lu J; Nombela-Arrieta C; Zhong J; Zhao L; Pivarnik G; Mondal S; Chai L; Silberstein LE; Luo HR. 2013. Deficiency of lipid phosphatase SHIP enables long-term reconstitution of hematopoietic inductive bone marrow microenvironment. Dev Cell 25(4):333-49. [PubMed: 23725762]  [MGI Ref ID J:198652]

Liu Q; Oliveira-Dos-Santos AJ; Mariathasan S; Bouchard D; Jones J; Sarao R; Kozieradzki I; Ohashi PS; Penninger JM; Dumont DJ. 1998. The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling. J Exp Med 188(7):1333-42. [PubMed: 9763612]  [MGI Ref ID J:72477]

Maxwell MJ; Duan M; Armes JE; Anderson GP; Tarlinton DM; Hibbs ML. 2011. Genetic segregation of inflammatory lung disease and autoimmune disease severity in SHIP-1-/- mice. J Immunol 186(12):7164-75. [PubMed: 21572033]  [MGI Ref ID J:175479]

Maxwell MJ; Yuan Y; Anderson KE; Hibbs ML; Salem HH; Jackson SP. 2004. SHIP1 and Lyn Kinase Negatively Regulate Integrin alpha IIb beta 3 signaling in platelets. J Biol Chem 279(31):32196-204. [PubMed: 15166241]  [MGI Ref ID J:91755]

Mondal S; Subramanian KK; Sakai J; Bajrami B; Luo HR. 2012. Phosphoinositide lipid phosphatase SHIP1 and PTEN coordinate to regulate cell migration and adhesion. Mol Biol Cell 23(7):1219-30. [PubMed: 22323291]  [MGI Ref ID J:196999]

Moon JB; Kim JH; Kim K; Youn BU; Ko A; Lee SY; Kim N. 2012. Akt induces osteoclast differentiation through regulating the GSK3beta/NFATc1 signaling cascade. J Immunol 188(1):163-9. [PubMed: 22131333]  [MGI Ref ID J:180812]

Nguyen NY; Maxwell MJ; Ooms LM; Davies EM; Hilton AA; Collinge JE; Hilton DJ; Kile BT; Mitchell CA; Hibbs ML; Jane SM; Curtis DJ. 2011. An ENU-induced mouse mutant of SHIP1 reveals a critical role of the stem cell isoform for suppression of macrophage activation. Blood 117(20):5362-71. [PubMed: 21421839]  [MGI Ref ID J:173266]

Nishio M; Watanabe K; Sasaki J; Taya C; Takasuga S; Iizuka R; Balla T; Yamazaki M; Watanabe H; Itoh R; Kuroda S; Horie Y; Forster I; Mak TW; Yonekawa H; Penninger JM; Kanaho Y; Suzuki A; Sasaki T. 2007. Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat Cell Biol 9(1):36-44. [PubMed: 17173042]  [MGI Ref ID J:126426]

Roongapinun S; Oh SY; Wu F; Panthong A; Zheng T; Zhu Z. 2010. Role of SHIP-1 in the adaptive immune responses to aeroallergen in the airway. PLoS One 5(11):e14174. [PubMed: 21151496]  [MGI Ref ID J:167280]

Severin S; Gratacap MP; Lenain N; Alvarez L; Hollande E; Penninger JM; Gachet C; Plantavid M; Payrastre B. 2007. Deficiency of Src homology 2 domain-containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth. J Clin Invest 117(4):944-52. [PubMed: 17347685]  [MGI Ref ID J:121283]

Tsantikos E; Maxwell MJ; Kountouri N; Harder KW; Tarlinton DM; Hibbs ML. 2012. Genetic interdependence of Lyn and negative regulators of B cell receptor signaling in autoimmune disease development. J Immunol 189(4):1726-36. [PubMed: 22798664]  [MGI Ref ID J:189750]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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 from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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