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   Donating Investigator Dr. Dan Dumont,   Sunnybrook Health Center

Appearance
white-bellied agouti
Related Genotype: A^w/?

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

Phenotype

Phenotype Information

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.

Inpp5d^tm1Dmt/Inpp5d^tm1Dmt

        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
• 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)

Inpp5d^tm1Dmt/Inpp5d^tm1Dmt

        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)

Inpp5d^tm1Dmt/Inpp5d^tm1Dmt

        B6.129P2/OlaHsd-Inpp5d^tm1Dmt

• 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)
• cellular phenotype
• decreased pre-B cell number
  • reduced pre-B cells in bone marrow at 10 weeks of age   (MGI Ref ID J:173266)

View Research Applications

Research Applications

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

Inpp5d^tm1Dmt 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 (knock-out)
Common Name(s)		SHIP-1-; SHIP1-; Ship -;
Mutation Made By		Dr. Dan Dumont,   Sunnybrook Health Center
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/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; 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

Inpp5d^tm1Dmt, 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

Inpp5d^tm1Dmt 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]

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]

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.

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

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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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