Strain Name:

C57BL/6J-Ptpn6me/SzJ

Stock Number:

010825

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Mice homozygous for the motheaten spontaneous mutation (Ptpn6me) develop severe autoimmune disease. Characteristics include granulocytic skin lesions, pneumonitis, impaired humoral and cell-mediated immune responses, decreased responses to T cell and B cell mitogens, deficient cytotoxic T cell and NK cell activity, as well as osteoporosis.

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 Coisogenic; Mutant Strain; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
 
Donating InvestigatorDr. Leonard D. Shultz,   The Jackson Laboratory

Description
Mice homozygous for the motheaten spontaneous mutation (Ptpn6me) develop severe autoimmune disease. Characteristics include granulocytic skin lesions, pneumonitis, impaired humoral and cell-mediated immune responses, decreased responses to T cell and B cell mitogens and deficient cytotoxic T cell and NK cell activity. B cells are LY-1+. Homozygous mutant mice also exhibit hyperimmunoglobulinemia, and express multiple autoantibodies. Macrophages show increased proliferative capacity. In addition to defects in the immune system, motheaten mice show classic symptoms of osteoporosis due to an increased number and activity of osteoclasts in the bone marrow. The lifespan of homozygous motheaten mice is approximately 3 weeks with death attributed to an autoimmune pneumonitis.

Development
The motheaten spontaneous mutation arose in C57BL/6J in 1965 in the Production Colony of The Jackson Laboratory.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Ptpn6me allele
000225   C3FeLe.B6 a/a-Ptpn6me/J
View Strains carrying   Ptpn6me     (1 strain)

Strains carrying other alleles of Ptpn6
008336   B6.129P2-Ptpn6tm1Rsky/J
000811   C57BL/6J-Ptpn6me-v/J
View Strains carrying other alleles of Ptpn6     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ptpn6me/Ptpn6me

        C57BL/6J-Ptpn6me/J
  • mortality/aging
  • partial preweaning lethality
    • high mortality before weaning   (MGI Ref ID J:5579)
  • pigmentation phenotype
  • abnormal skin pigmentation
    • recognized at 3 to 4 days of age by patchy absence of skin pigment   (MGI Ref ID J:5579)
  • immune system phenotype
  • abnormal Peyer's patch morphology
    • rarely any differentiation of lymphoid tissue into nodules is found   (MGI Ref ID J:5579)
    • lymphocytes are larger and sparsely distributed   (MGI Ref ID J:5579)
  • abnormal humoral immune response
    • mice are deficient in capacity for immune response   (MGI Ref ID J:5579)
    • increased immunoglobulin level   (MGI Ref ID J:5579)
      • increased IgA level
        • serum levels are elevated   (MGI Ref ID J:5579)
      • increased IgG level
        • serum levels are elevated   (MGI Ref ID J:5579)
      • increased IgM level
        • serum levels are markedly elevated above normal   (MGI Ref ID J:5579)
  • abnormal immune system cell morphology
    • mice have a population of unusual binucleate lymphocytes   (MGI Ref ID J:5579)
    • abnormal granulocyte morphology
      • differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population   (MGI Ref ID J:5579)
    • abnormal leukocyte cell number   (MGI Ref ID J:5579)
      • increased leukocyte cell number   (MGI Ref ID J:5579)
        • increased granulocyte number   (MGI Ref ID J:5579)
        • increased monocyte cell number   (MGI Ref ID J:5579)
  • abnormal thymus morphology   (MGI Ref ID J:5579)
    • small thymus
      • although smaller than normal, the thymus is histologically normal until 25 days of age   (MGI Ref ID J:5579)
      • severe involution and necrosis is found in sick mice, with severity correlating with degree of illness   (MGI Ref ID J:5579)
  • enlarged spleen   (MGI Ref ID J:5579)
  • hematopoietic system phenotype
  • abnormal granulocyte morphology
    • differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population   (MGI Ref ID J:5579)
  • abnormal leukocyte cell number   (MGI Ref ID J:5579)
    • increased leukocyte cell number   (MGI Ref ID J:5579)
      • increased granulocyte number   (MGI Ref ID J:5579)
      • increased monocyte cell number   (MGI Ref ID J:5579)
  • abnormal thymus morphology   (MGI Ref ID J:5579)
    • small thymus
      • although smaller than normal, the thymus is histologically normal until 25 days of age   (MGI Ref ID J:5579)
      • severe involution and necrosis is found in sick mice, with severity correlating with degree of illness   (MGI Ref ID J:5579)
  • enlarged spleen   (MGI Ref ID J:5579)
  • respiratory system phenotype
  • abnormal lung morphology
    • mice develop lesions in the lung by 3 days of age   (MGI Ref ID J:5579)
  • cellular phenotype
  • abnormal cell cycle   (MGI Ref ID J:66843)
    • abnormal cell cycle checkpoint function
      • there is a higher than normal percentage of splenocytes in S and G2/M (22% instead of 7%) and corresponding decrease in splenocytes in G0/G1 (73% instead of 89%)   (MGI Ref ID J:66843)
      • 6 hours after 5 Gy of gamma irradiation homozygous splenocytes show abnormal cell cycle arrest, with 31% instead of the wild-type 4% in S+G2/M phases, and fewer irradiated splenocytes are found in the subG0 (hyplodiploid) state (15% instead of 45%)   (MGI Ref ID J:66843)
  • decreased apoptosis
    • only 21% of spleen cells are apoptotic 6 hours after exposure to 5 Gy gamma irradiation, whereas 40% of wildtype splenocytes are apoptotic after treatment.   (MGI Ref ID J:66843)
    • B and T cells show the greatest resistance to apoptosis in the splenocyte population, but all splenic cell types including macrophages and granulocytes have greater resistance to apoptosis than wildtype cells   (MGI Ref ID J:66843)
    • splenocytoes from homozygotes have much less disruption of mitochondrial transmembrane potential at 6 and 24 hours post-exposure to 5 Gy of gamma irradiation and do not show the normal increase in expression of Bax   (MGI Ref ID J:66843)
  • decreased cellular sensitivity to gamma-irradiation
    • the LD50 for homozygous spleen cells is 24.5 Gy gamma radiation versus 6.5 Gy for wildtype splenocytes   (MGI Ref ID J:66843)
  • integument phenotype
  • abnormal skin pigmentation
    • recognized at 3 to 4 days of age by patchy absence of skin pigment   (MGI Ref ID J:5579)
  • focal hair loss
    • patchy absence of hair in the coat gives mice a motheaten appearance   (MGI Ref ID J:5579)
  • skin lesions
    • rapidly progressing lesions develop on the feet by 3 weeks of age   (MGI Ref ID J:5579)
    • as early as 2 days after birth abscesses appear on the skin, rupture and begin to heal in 24 hrs   (MGI Ref ID J:5579)

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

Ptpn6me/Ptpn6me

        involves: C3H/HeN * C57BL/6J * NFS
  • mortality/aging
  • premature death
    • life span about 8 weeks whereas on a C57BL/6 background survival is about 3 weeks   (MGI Ref ID J:30994)
    • occasional survival to 16 weeks on an NFS or C3H background for larger individuals   (MGI Ref ID J:30994)
  • growth/size phenotype
  • decreased body weight
    • weigh about 66% of control weight   (MGI Ref ID J:30994)
  • limbs/digits/tail phenotype
  • absent limbs
    • autoamputation of 2-3 extremities by 8 weeks of age   (MGI Ref ID J:30994)
  • integument phenotype
  • abnormal skin condition
    • cutaneous granulomatous lesions at 8 weeks   (MGI Ref ID J:30994)
  • cellular phenotype
  • increased splenocyte proliferation
    • lack of stimulatory effect of ConA   (MGI Ref ID J:30994)
  • hematopoietic system phenotype
  • increased splenocyte proliferation
    • lack of stimulatory effect of ConA   (MGI Ref ID J:30994)
  • immune system phenotype
  • increased IgM level
    • increased secretion by splenocytes in culture   (MGI Ref ID J:30994)
    • serum levels elevated relative to controls   (MGI Ref ID J:30994)
  • increased autoantibody level   (MGI Ref ID J:30994)
  • increased splenocyte proliferation
    • lack of stimulatory effect of ConA   (MGI Ref ID J:30994)

Ptpn6me/Ptpn6me

        involves: C3HeB/FeJ * C57BL/6
  • mortality/aging
  • complete postnatal lethality
    • death at around 3 weeks of age involving intra alveolar hemorrhage   (MGI Ref ID J:72655)
  • growth/size phenotype
  • decreased body weight
    • about half of controls   (MGI Ref ID J:72655)
  • nervous system phenotype
  • abnormal myelination
    • decreased   (MGI Ref ID J:72655)
  • abnormal nervous system morphology   (MGI Ref ID J:72655)
    • abnormal CNS glial cell morphology   (MGI Ref ID J:72655)
      • abnormal astrocyte morphology
        • GFAP+ astrocytes decreased about 50% on both the hippocampus and the forebrain fiber tracts   (MGI Ref ID J:72655)
      • abnormal microglial cell morphology
        • F4/80+ microglial cells are reduced in number   (MGI Ref ID J:72655)
    • abnormal forebrain morphology   (MGI Ref ID J:72655)
      • abnormal hippocampus CA1 region morphology
        • about 20% more neurons present   (MGI Ref ID J:72655)
      • abnormal hippocampus development
        • scattered areas of focal necrosis   (MGI Ref ID J:72655)
      • abnormal telencephalon development
        • scattered areas of focal necrosis in the cortex   (MGI Ref ID J:72655)
    • decreased brain size
      • length and width decreased   (MGI Ref ID J:72655)
      • weight normal   (MGI Ref ID J:72655)
  • respiratory system phenotype
  • abnormal pulmonary alveolar system morphology
    • intra alveolar hemorrhage around 3 weeks of age leading to death   (MGI Ref ID J:72655)
  • hematopoietic system phenotype
  • abnormal microglial cell morphology
    • F4/80+ microglial cells are reduced in number   (MGI Ref ID J:72655)
  • immune system phenotype
  • abnormal microglial cell morphology
    • F4/80+ microglial cells are reduced in number   (MGI Ref ID J:72655)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Autoimmunity

Internal/Organ Research
Skeleton
      Bone

Ptpn6me related

Apoptosis Research

Dermatology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Thyroid Defects

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
Immunodeficiency
Inflammation

Internal/Organ Research
Lymphoid Tissue Defects
Spleen Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ptpn6me
Allele Name motheaten
Allele Type Spontaneous
Common Name(s) SHP-1 deficient; me;
Strain of OriginC57BL/6J
Gene Symbol and Name Ptpn6, protein tyrosine phosphatase, non-receptor type 6
Chromosome 6
Gene Common Name(s) HCP; HCPH; HPTP1C; Hcph; PTP-1C; Ptp1C; SH-PTP1; SHP-1; SHP-1L; SHP1; Spin; hemopoietic cell phosphatase; me; motheaten;
General Note Homozygotes are characterized by early onset autoimmunity and severe immunodeficiency (J:5579). Mice develop an unusual pneumonia which progresses to accumulation of crystal-containing macrophages in the alveoli (J:5999). Spleen macrophages of homozygotes have an accelerated rate of proliferation which may contribute to the pulmonary disease (J:7274). The number of surface-Ig-bearing lymphocytes (B-cells) is greatly reduced, and the B-cells present are of immature rather than adult type (J:6065). The number of T-cells is normal, but several T-cell functions are defective. Natural killer cell activity is virtually absent (J:6485).

Genbank ID for this mutation: S63764

Molecular Note A single nucleotide (C) deletion at position 228 creates a cryptic splice site. This results in the deletion of a 101bp segment in the encoded transcript, and a frameshift in the encoded protein. [MGI Ref ID J:11892] [MGI Ref ID J:60297]

Genotyping

Genotyping Information

Genotyping Protocols

Ptpn6me, Restriction Enzyme Digest


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Green MC; Shultz LD. 1975. Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J Hered 66(5):250-8. [PubMed: 1184950]  [MGI Ref ID J:5579]

Additional References

Ptpn6me related

Abram CL; Roberge GL; Pao LI; Neel BG; Lowell CA. 2013. Distinct roles for neutrophils and dendritic cells in inflammation and autoimmunity in motheaten mice. Immunity 38(3):489-501. [PubMed: 23521885]  [MGI Ref ID J:195276]

Aloulou M; Ben Mkaddem S; Biarnes-Pelicot M; Boussetta T; Souchet H; Rossato E; Benhamou M; Crestani B; Zhu Z; Blank U; Launay P; Monteiro RC. 2012. IgG1 and IVIg induce inhibitory ITAM signaling through FcgammaRIII controlling inflammatory responses. Blood 119(13):3084-96. [PubMed: 22337713]  [MGI Ref ID J:182509]

Berg KL; Siminovitch KA; Stanley ER. 1999. SHP-1 regulation of p62(DOK) tyrosine phosphorylation in macrophages. J Biol Chem 274(50):35855-65. [PubMed: 10585470]  [MGI Ref ID J:58900]

Bignon JS; Siminovitch KA. 1994. Identification of PTP1C mutation as the genetic defect in motheaten and viable motheaten mice: a step toward defining the roles of protein tyrosine phosphatases in the regulation of hemopoietic cell differentiation and function. Clin Immunol Immunopathol 73(2):168-79. [PubMed: 7923924]  [MGI Ref ID J:21151]

Bonaparte KL; Hudson CA; Wu C; Massa PT. 2006. Inverse regulation of inducible nitric oxide synthase (iNOS) and arginase I by the protein tyrosine phosphatase SHP-1 in CNS glia. Glia 53(8):827-35. [PubMed: 16565987]  [MGI Ref ID J:156128]

Carter JD; Calabrese GM; Naganuma M; Lorenz U. 2005. Deficiency of the Src homology region 2 domain-containing phosphatase 1 (SHP-1) causes enrichment of CD4+CD25+ regulatory T cells. J Immunol 174(11):6627-38. [PubMed: 15905501]  [MGI Ref ID J:99043]

Carter JD; Neel BG; Lorenz U. 1999. The tyrosine phosphatase SHP-1 influences thymocyte selection by setting TCR signaling thresholds. Int Immunol 11(12):1999-2014. [PubMed: 10590266]  [MGI Ref ID J:59134]

Christophi GP; Hudson CA; Panos M; Gruber RC; Massa PT. 2009. Modulation of macrophage infiltration and inflammatory activity by the phosphatase SHP-1 in virus-induced demyelinating disease. J Virol 83(2):522-39. [PubMed: 18987138]  [MGI Ref ID J:153390]

Clark EA; Shultz LD; Pollack SB. 1981. Mutations in mice that influence natural killer (NK) cell activity. Immunogenetics 12(5-6):601-13. [PubMed: 6971254]  [MGI Ref ID J:6485]

Croker BA; Lawson BR; Berger M; Eidenschenk C; Blasius AL; Moresco EM; Sovath S; Cengia L; Shultz LD; Theofilopoulos AN; Pettersson S; Beutler BA. 2008. Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger. Proc Natl Acad Sci U S A 105(39):15028-33. [PubMed: 18806225]  [MGI Ref ID J:142845]

Davidson D; Bakinowski M; Thomas ML; Horejsi V; Veillette A. 2003. Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor. Mol Cell Biol 23(6):2017-28. [PubMed: 12612075]  [MGI Ref ID J:113969]

Fowler CC; Pao LI; Blattman JN; Greenberg PD. 2010. SHP-1 in T cells limits the production of CD8 effector cells without impacting the formation of long-lived central memory cells. J Immunol 185(6):3256-67. [PubMed: 20696858]  [MGI Ref ID J:163839]

Hsu HC; Shultz LD; Su X; Shi J; Yang PA; Relyea MJ; Zhang HG; Mountz JD. 2001. Mutation of the hematopoietic cell phosphatase (Hcph) gene is associated with resistance to gamma-irradiation-induced apoptosis in Src homology protein tyrosine phosphatase (SHP)-1-deficient 'motheaten' mutant mice. J Immunol 166(2):772-80. [PubMed: 11145649]  [MGI Ref ID J:66843]

Inoue T; Suzuki Y; Mizuno K; Nakata K; Yoshimaru T; Ra C. 2009. SHP-1 exhibits a pro-apoptotic function in antigen-stimulated mast cells: positive regulation of mitochondrial death pathways and negative regulation of survival signaling pathways. Mol Immunol 47(2-3):222-32. [PubMed: 19875169]  [MGI Ref ID J:155341]

Iype T; Sankarshanan M; Mauldin IS; Mullins DW; Lorenz U. 2010. The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells. J Immunol 185(10):6115-27. [PubMed: 20952680]  [MGI Ref ID J:165785]

Jiao H; Yang W; Berrada K; Tabrizi M; Shultz L; Yi T. 1997. Macrophages from motheaten and viable motheaten mutant mice show increased proliferative responses to GM-CSF: detection of potential HCP substrates in GM-CSF signal transduction. Exp Hematol 25(7):592-600. [PubMed: 9216734]  [MGI Ref ID J:41396]

Johnson KG; LeRoy FG; Borysiewicz LK; Matthews RJ. 1999. TCR signaling thresholds regulating T cell development and activation are dependent upon SHP-1. J Immunol 162(7):3802-13. [PubMed: 10201897]  [MGI Ref ID J:53576]

Kamata T; Yamashita M; Kimura M; Murata K; Inami M; Shimizu C; Sugaya K; Wang CR; Taniguchi M; Nakayama T. 2003. src homology 2 domain-containing tyrosine phosphatase SHP-1 controls the development of allergic airway inflammation. J Clin Invest 111(1):109-19. [PubMed: 12511594]  [MGI Ref ID J:81122]

Kon-Kozlowski M; Pani G; Pawson T; Siminovitch KA. 1996. The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells. J Biol Chem 271(7):3856-62. [PubMed: 8632004]  [MGI Ref ID J:31423]

Kozlowski M; Mlinaric-Rascan I; Feng GS; Shen R; Pawson T; Siminovitch KA. 1993. Expression and catalytic activity of the tyrosine phosphatase PTP1C is severely impaired in motheaten and viable motheaten mice. J Exp Med 178(6):2157-63. [PubMed: 8245788]  [MGI Ref ID J:15725]

Kruger J; Butler JR; Cherapanov V; Dong Q; Ginzberg H; Govindarajan A; Grinstein S; Siminovitch KA; Downey GP. 2000. Deficiency of Src homology 2-containing phosphatase 1 results in abnormalities in murine neutrophil function: studies in motheaten mice. J Immunol 165(10):5847-59. [PubMed: 11067945]  [MGI Ref ID J:118386]

Kuntz L; Jachez B; Roman D; Loor F. 1993. Modulation of adoptively transferred viable motheaten pathology in sublethally irradiated normal recipient mice by normal hematopoietic cells. Cell Immunol 146(1):215-21. [PubMed: 8093859]  [MGI Ref ID J:3800]

Lorenz U; Bergemann AD; Steinberg HN; Flanagan JG; Li X; Galli SJ; Neel BG. 1996. Genetic analysis reveals cell type-specific regulation of receptor tyrosine kinase c-Kit by the protein tyrosine phosphatase SHP1. J Exp Med 184(3):1111-26. [PubMed: 9064328]  [MGI Ref ID J:35276]

Lutzner MA; Hansen CT. 1976. Motheater: an immunodeficient mouse with markedly less ability to survive that the nude mouse in a germfree environment. J Immunol 116(5):1496-7. [PubMed: 1270804]  [MGI Ref ID J:5648]

Lyons BL; Smith RS; Hurd RE; Hawes NL; Burzenski LM; Nusinowitz S; Hasham MG; Chang B; Shultz LD. 2006. Deficiency of SHP-1 protein-tyrosine phosphatase in 'viable motheaten' mice results in retinal degeneration. Invest Ophthalmol Vis Sci 47(3):1201-9. [PubMed: 16505059]  [MGI Ref ID J:108375]

Martin A; Tsui HW; Tsui FW. 1999. SHP-1 variant proteins are absent in motheaten mice despite presence of splice variant transcripts with open reading frames. Mol Immunol 36(15-16):1029-41. [PubMed: 10698306]  [MGI Ref ID J:60297]

Mauldin IS; Tung KS; Lorenz UM. 2012. The tyrosine phosphatase SHP-1 dampens murine Th17 development. Blood 119(19):4419-29. [PubMed: 22438258]  [MGI Ref ID J:185170]

McCoy KL; Clagett J; Rosse C. 1985. Effects of the motheaten gene on murine B-cell production. Exp Hematol 13(6):554-9. [PubMed: 3873348]  [MGI Ref ID J:7856]

McCoy KL; Nielson K; Clagett J. 1984. Spontaneous production of colony-stimulating activity by splenic Mac-1 antigen-positive cells from autoimmune motheaten mice. J Immunol 132(1):272-6. [PubMed: 6361123]  [MGI Ref ID J:7274]

Mlinaric-Rascan I; Asa SL; Siminovitch KA. 1994. Increased expression of the stefin A cysteine proteinase inhibitor occurs in the myelomonocytic cell-infiltrated tissues of autoimmune motheaten mice. Am J Pathol 145(4):902-12. [PubMed: 7943179]  [MGI Ref ID J:20878]

Nakamura MC; Niemi EC; Fisher MJ; Shultz LD; Seaman WE; Ryan JC. 1997. Mouse Ly-49A interrupts early signaling events in natural killer cell cytotoxicity and functionally associates with the SHP-1 tyrosine phosphatase. J Exp Med 185(4):673-84. [PubMed: 9034146]  [MGI Ref ID J:38943]

Nakata K; Suzuki Y; Inoue T; Ra C; Yakura H; Mizuno K. 2011. Deficiency of SHP1 leads to sustained and increased ERK activation in mast cells, thereby inhibiting IL-3-dependent proliferation and cell death. Mol Immunol 48(4):472-80. [PubMed: 21044800]  [MGI Ref ID J:167059]

Nakata K; Yoshimaru T; Suzuki Y; Inoue T; Ra C; Yakura H; Mizuno K. 2008. Positive and negative regulation of high affinity IgE receptor signaling by Src homology region 2 domain-containing phosphatase 1. J Immunol 181(8):5414-24. [PubMed: 18832698]  [MGI Ref ID J:140765]

Napolitano A; Pittoni P; Beaudoin L; Lehuen A; Voehringer D; Macdonald HR; Dellabona P; Casorati G. 2013. Functional Education of Invariant NKT Cells by Dendritic Cell Tuning of SHP-1. J Immunol 190(7):3299-308. [PubMed: 23427253]  [MGI Ref ID J:194522]

Nesterovitch AB; Szanto S; Gonda A; Bardos T; Kis-Toth K; Adarichev VA; Olasz K; Ghassemi-Najad S; Hoffman MD; Tharp MD; Mikecz K; Glant TT. 2011. Spontaneous insertion of a b2 element in the ptpn6 gene drives a systemic autoinflammatory disease in mice resembling neutrophilic dermatosis in humans. Am J Pathol 178(4):1701-14. [PubMed: 21435452]  [MGI Ref ID J:169850]

Paulson RF; Vesely S; Siminovitch KA; Bernstein A. 1996. Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1. Nat Genet 13(3):309-15. [PubMed: 8673130]  [MGI Ref ID J:34290]

Rego D; Kumar A; Nilchi L; Wright K; Huang S; Kozlowski M. 2011. IL-6 production is positively regulated by two distinct Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1)-dependent CCAAT/enhancer-binding protein beta and NF-kappaB pathways and an SHP-1-independent NF-kappaB pathway in lipopolysaccharide-stimulated bone marrow-derived macrophages. J Immunol 186(9):5443-56. [PubMed: 21422245]  [MGI Ref ID J:172869]

Sathish JG; Dolton G; Leroy FG; Matthews RJ. 2007. Loss of Src homology region 2 domain-containing protein tyrosine phosphatase-1 increases CD8+ T cell-APC conjugate formation and is associated with enhanced in vivo CTL function. J Immunol 178(1):330-7. [PubMed: 17182570]  [MGI Ref ID J:141929]

Sathish JG; Walters J; Luo JC; Johnson KG; Leroy FG; Brennan P; Kim KP; Gygi SP; Neel BG; Matthews RJ. 2004. CD22 is a functional ligand for SH2 domain-containing protein-tyrosine phosphatase-1 in primary T cells. J Biol Chem 279(46):47783-91. [PubMed: 15364920]  [MGI Ref ID J:118518]

Scribner CL; Hansen CT; Klinman DM; Steinberg AD. 1987. The interaction of the xid and me genes. J Immunol 138(11):3611-7. [PubMed: 2884254]  [MGI Ref ID J:30994]

Shultz LD; Bailey CL; Coman DR. 1983. Hematopoietic stem cell function in motheaten mice. Exp Hematol 11(7):667-80. [PubMed: 6350031]  [MGI Ref ID J:7162]

Shultz LD; Green MC. 1976. Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins. J Immunol 116(4):936-43. [PubMed: 56406]  [MGI Ref ID J:5624]

Shultz LD; Rajan TV; Greiner DL. 1997. Severe defects in immunity and hematopoiesis caused by SHP-1 protein-tyrosine-phosphatase deficiency. Trends Biotechnol 15(8):302-7. [PubMed: 9263478]  [MGI Ref ID J:42157]

Shultz LD; Schweitzer PA; Rajan TV; Yi T; Ihle JN; Matthews RJ; Thomas ML; Beier DR. 1993. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 73(7):1445-54. [PubMed: 8324828]  [MGI Ref ID J:14935]

Sidman CL; Shultz LD; Unanue ER. 1978. The mouse mutant motheaten. II. Functional studies of the immune system. J Immunol 121(6):2399-404. [PubMed: 363947]  [MGI Ref ID J:6065]

Sundberg JP (ed.). 1994. Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. In: Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. CRC Press, Boca Raton.  [MGI Ref ID J:30359]

Takeoka Y; Chen SY; Boyd RL; Tsuneyama K; Taguchi N; Morita S; Yago H; Suehiro S; Ansari AA; Shultz LD; Gershwin ME. 1997. A comparative analysis of the murine thymic microenvironment in normal, autoimmune, and immunodeficiency states. Dev Immunol 5(2):79-89. [PubMed: 9587708]  [MGI Ref ID J:44504]

Tsui FW; Tsui HW. 1994. Molecular basis of the motheaten phenotype. Immunol Rev 138:185-206. [PubMed: 8070815]  [MGI Ref ID J:18549]

Tsui HW; Siminovitch KA; de Souza L; Tsui FW. 1993. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet 4(2):124-9. [PubMed: 8348149]  [MGI Ref ID J:11892]

Umeda S; Beamer WG; Takagi K; Naito M; Hayashi S; Yonemitsu H; Yi T; Shultz LD. 1999. Deficiency of SHP-1 protein-tyrosine phosphatase activity results in heightened osteoclast function and decreased bone density. Am J Pathol 155(1):223-33. [PubMed: 10393854]  [MGI Ref ID J:108187]

Ward JM. 1978. Pulmonary pathology of the motheaten mouse. Vet Pathol 15(2):170-8. [PubMed: 664185]  [MGI Ref ID J:5999]

Wishcamper CA; Coffin JD; Lurie DI. 2001. Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the motheaten (me/me) mouse brain. J Comp Neurol 441(2):118-33. [PubMed: 11745639]  [MGI Ref ID J:72655]

Yang W; Mckenna SD; Jiao H; Tabrizi M; Lynes MA; Shultz LD; Yi T. 1998. SHP-1 deficiency in B-lineage cells is associated with heightened lyn protein expression and increased lyn kinase activity. Exp Hematol 26(12):1126-32. [PubMed: 9808051]  [MGI Ref ID J:51142]

Zhao J; Brooks DM; Lurie DI. 2006. Lipopolysaccharide-activated SHP-1-deficient motheaten microglia release increased nitric oxide, TNF-alpha, and IL-1beta. Glia 53(3):304-12. [PubMed: 16265671]  [MGI Ref ID J:156147]

Zhao J; Lurie DI. 2004. Cochlear ablation in mice lacking SHP-1 results in an extended period of cell death of anteroventral cochlear nucleus neurons. Hear Res 189(1-2):63-75. [PubMed: 14987753]  [MGI Ref ID J:88807]

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 maintaining a live colony, these mice can be bred as heterozygotes. The lifespan of homozygous motheaten mice is approximately 3 weeks with death attributed to an autoimmune pneumonitis.

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* $2250.00
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* $2925.00
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.

General Supply Notes

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  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.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

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

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

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


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