Description

Strain Information

Former Names C57BL/6J-Hcphme-v/J    (Changed: 16-JUN-05 ) Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Heterozygote         (Female x Male)   29-SEP-09 Species laboratory mouse H2 Haplotype b Generation N42F6 (21-DEC-10) Generation Definitions

Appearance
black, affected (bare spots)
Related Genotype: a/a Ptpn6^me-v/Ptpn6^me-v

black, unaffected
Related Genotype: a/a Ptpn6^me-v/+ or a/a +/?

Description
Mice homozygous for the viable motheaten spontaneous mutation (Ptpn6^me-v) develop severe autoimmune disease. Characteristics include by 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, viable motheaten mice show classic symptoms of osteoporosis due to an increased number and activity of osteoclasts in the bone marrow. The osteoporosis phenotype includes significantly lower bone mineral density and mineral content in the femurs of viable motheaten mice compared to normal littermate controls. In addition, these mice show reduced amounts of trabecular bone and decreased cortical thickness. The lifespan of homozygous viable motheaten mice is approximately 9 weeks with death attributed to an autoimmune pneumonitis.

Control Information

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

Related Strains

Strains carrying other alleles of Ptpn6

008336	B6.129P2-Ptpn6tm1Rsky/J
000225	C3FeLe.B6 a/a-Ptpn6me/J
010825	C57BL/6J-Ptpn6me/SzJ

View Strains carrying other alleles of Ptpn6     (3 strains)

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ptpn6^me-v/Ptpn6^me-v

        C57BL/6J-Ptpn6^me-v

• mortality/aging
• premature death
  • mice die at about 9 weeks instead of at 3 weeks as in Ptpn6^me homozygotes   (MGI Ref ID J:7531)
  • death is due to a progressive and fatal autoimmune syndrome   (MGI Ref ID J:7531)
• immune system phenotype
• abnormal immunoglobulin level
  • uncontrolled levels   (MGI Ref ID J:7665)
• abnormal inflammatory response
  • resembles rheumatoid arthritis   (MGI Ref ID J:20845)
  • immunosuppressant drugs inhibit arthritic symptoms, but non-steroid anti-inflammatory drugs do not   (MGI Ref ID J:20845)
• • chronic inflammation
    • reactions in the paws consist mainly of polymorphonuclear and mononuclear cell infiltration in the subcutaneous tissue extending to the periosteum and joint   (MGI Ref ID J:20845)
    • paws become deformed causing progressive problems walking   (MGI Ref ID J:20845)
  • interstitial pneumonia
    • pneumonitis progression is slower than in Ptpn6^me homozygotes but still causes death   (MGI Ref ID J:7531)
  • rheumatoid arthritis   (MGI Ref ID J:20845)
• decreased B cell number
  • lambda1 and lambda2, 3 B cells are reduced 14- and 4-fold, respectively, in the spleen and 5.9- and 2.2-fold, respectively, in the bone marrow compared to B cell numbers in wild-type mice   (MGI Ref ID J:113218)
• • decreased mature B cell number
    • a result of a rapid expansion of the plasma cell population   (MGI Ref ID J:7905)
• increased plasma cell number
  • due to a factor in serum of mutant mice that increases cell maturation by three orders of magnitude   (MGI Ref ID J:7905)
• respiratory system phenotype
• interstitial pneumonia
  • pneumonitis progression is slower than in Ptpn6^me homozygotes but still causes death   (MGI Ref ID J:7531)
• growth/size phenotype
• decreased body size   (MGI Ref ID J:113218)
• hematopoietic system phenotype
• decreased B cell number
  • lambda1 and lambda2, 3 B cells are reduced 14- and 4-fold, respectively, in the spleen and 5.9- and 2.2-fold, respectively, in the bone marrow compared to B cell numbers in wild-type mice   (MGI Ref ID J:113218)
• • decreased mature B cell number
    • a result of a rapid expansion of the plasma cell population   (MGI Ref ID J:7905)
• increased plasma cell number
  • due to a factor in serum of mutant mice that increases cell maturation by three orders of magnitude   (MGI Ref ID J:7905)
• pigmentation phenotype
• absent skin pigmentation
  • at 3-4 days of age mice have focal depigmentation of the skin   (MGI Ref ID J:20845)
• skeleton phenotype
• rheumatoid arthritis   (MGI Ref ID J:20845)
• integument phenotype
• abnormal skin condition   (MGI Ref ID J:113218)
• absent skin pigmentation
  • at 3-4 days of age mice have focal depigmentation of the skin   (MGI Ref ID J:20845)
• focal hair loss
  • patchy absence of hair follows focal skin depigmentation giving the coat an uneven or motheaten appearance   (MGI Ref ID J:20845)
• spontaneous skin ulceration
  • necrotic lesions can develop on paws, tail and ears   (MGI Ref ID J:20845)

View Research Applications

Research Applications

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

Internal/Organ Research
Skeleton
      Bone

Ptpn6^me-v related

Dermatology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Thyroid Defects

Hematological Research

Immunology and Inflammation Research
Autoimmunity
Inflammation

Internal/Organ Research
Lymphoid Tissue Defects
Spleen Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ptpn6me-v
Allele Name		viable motheaten
Allele Type		Spontaneous
Common Name(s)		Hcphme-v; mev; mev; motheaten viable;
Strain of Origin		C57BL/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; Ptph6; SH-PTP1; SHP-1; SHP-1L; SHP1; Spin; hemopoietic cell phosphatase; me; motheaten;
General Note		Large numbers of atypical plasma cells called "Mott" cells occur in lymphoid tissues of homozygous mutants. These cells contain inclusions called "Russell bodies" that consist of crystallized immunoglobulin (J:14936). Hcphme-v/Hcphme-v mutant prothymocytes fail to populate the thymus of irradiated hosts. Mutant prothymocytes seed the irradiated thymus but do not proliferate or differentiate, due to a defect in activity of intrathymic accessory cells derived from bone marrow (J:16613). Like the autoimmune lymphoproliferation (Faslpr) and generalized lymphadenopathy disease (Faslgld) mutations, Hcphme-v displays a decreased response to T-cell mitogens. Exogenous recombinant interleukin 2 added to splenic cultures from Faslpr and Faslgld mice restored T cell proliferation in response to mitogens; interleukin 2 was not able to restore proliferation response in Hcphme-v cultures (J:1661). Expression of stefin A, a cysteine protease inhibitor, increases in bone marrow, spleen, and pulmonary tissue of motheaten and viable motheaten mice, along with increased levels of the myelomonocytic cells that produce the stefins (J:20878).
Molecular Note		A T-to-A transversion point mutation at a splice consensus site results in the use of two other cryptic sites. One site would result in five amino acids being deleted from the encoded protein and the other would include 69bp of intronic sequence in the transcript. [MGI Ref ID J:11892]

Genotyping

Genotyping Information

Genotyping Protocols

Ptpn6^me-v , Pyrosequencing
Ptpn6^me-v, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Froidevaux S; Kuntz L; Velin D; Loor F. 1991. Different nature of the proliferation defects of GLD, LPR and MEV C57BL/6 mouse lymphoid cells. Autoimmunity 10(3):233-40. [PubMed: 1756226]  [MGI Ref ID J:1661]

Joliat MJ; Lang PA; Lyons BL; Burzenski L; Lynes MA; Yi T; Sundberg JP; Shultz LD. 2002. Absence of CD5 Dramatically Reduces Progression of Pulmonary Inflammatory Lesions in SHP-1 Protein-Tyrosine Phosphatase-Deficient 'Viable Motheaten' Mice. J Autoimmun 18(2):105-17. [PubMed: 11908943]  [MGI Ref ID J:76141]

Kovarik J; Kuntz L; Ryffel B; Borel JF. 1994. The viable motheaten (mev) mouse--a new model for arthritis. J Autoimmun 7(5):575-88. [PubMed: 7840851]  [MGI Ref ID J:20845]

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]

Lyons BL; Lynes MA; Burzenski L; Joliat MJ; Hadjout N; Shultz LD. 2003. Mechanisms of anemia in SHP-1 protein tyrosine phosphatase-deficient 'viable motheaten' mice. Exp Hematol 31(3):234-43. [PubMed: 12644021]  [MGI Ref ID J:82283]

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]

Shultz LD; Coman DR; Bailey CL; Beamer WG; Sidman CL. 1984. Viable motheaten, a new allele at the motheaten locus. I. Pathology. Am J Pathol 116(2):179-92. [PubMed: 6380298]  [MGI Ref ID J:7531]

Shultz LD; Coman DR; Lyons BL; Sidman CL; Taylor S. 1987. Development of plasmacytoid cells with Russell bodies in autoimmune viable motheaten mice. Am J Pathol 127(1):38-50. [PubMed: 3551623]  [MGI Ref ID J:14936]

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; Marshall JD; Masiello NC; Roths JB; Shultz LD. 1984. Novel B-cell maturation factor from spontaneously autoimmune viable motheaten mice. Proc Natl Acad Sci U S A 81(22):7199-202. [PubMed: 6334306]  [MGI Ref ID J:7665]

Sidman CL; Shultz LD; Evans R. 1985. A serum-derived molecule from autoimmune viable motheaten mice potentiates the action of a B cell maturation factor. J Immunol 135(2):870-2. [PubMed: 3891855]  [MGI Ref ID J:7905]

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]

Van Zant G; Shultz L. 1989. Hematologic abnormalities of the immunodeficient mouse mutant, viable motheaten (mev). Exp Hematol 17(2):81-7. [PubMed: 2783574]  [MGI Ref ID J:14937]

Yu WM; Hawley TS; Hawley RG; Qu CK. 2002. Role of the docking protein Gab2 in beta(1)-integrin signaling pathway-mediated hematopoietic cell adhesion and migration. Blood 99(7):2351-9. [PubMed: 11895767]  [MGI Ref ID J:75835]

Ptpn6^me-v related

Abu-Dayyeh I; Hassani K; Westra ER; Mottram JC; Olivier M. 2010. Comparative study of the ability of Leishmania mexicana promastigotes and amastigotes to alter macrophage signaling and functions. Infect Immun 78(6):2438-45. [PubMed: 20368344]  [MGI Ref ID J:159974]

An H; Hou J; Zhou J; Zhao W; Xu H; Zheng Y; Yu Y; Liu S; Cao X. 2008. Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1. Nat Immunol 9(5):542-50. [PubMed: 18391954]  [MGI Ref ID J:134511]

Aoki K; Didomenico E; Sims NA; Mukhopadhyay K; Neff L; Houghton A; Amling M; Levy JB; Horne WC; Baron R. 1999. The tyrosine phosphatase SHP-1 is a negative regulator of osteoclastogenesis and osteoclast resorbing activity: increased resorption and osteopenia in me(v)/me(v) mutant mice. Bone 25(3):261-7. [PubMed: 10495129]  [MGI Ref ID J:59477]

Berg KL; Carlberg K; Rohrschneider LR; Siminovitch KA; Stanley ER. 1998. The major SHP-1-binding, tyrosine-phosphorylated protein in macrophages is a member of the KIR/LIR family and an SHP-1 substrate. Oncogene 17(19):2535-41. [PubMed: 9824165]  [MGI Ref ID J:51247]

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]

Cassady-Cain RL; Kaushik AK. 2006. Increased negative selection impairs neonatal B cell repertoire but does not directly lead to generation of disease-associated IgM auto-antibodies. Int Immunol 18(5):661-9. [PubMed: 16569683]  [MGI Ref ID J:108900]

Cho YS; Oh SY; Zhu Z. 2008. Tyrosine phosphatase SHP-1 in oxidative stress and development of allergic airway inflammation. Am J Respir Cell Mol Biol 39(4):412-9. [PubMed: 18441283]  [MGI Ref ID J:154284]

Cornall RJ; Cyster JG; Hibbs ML; Dunn AR; Otipoby KL; Clark EA; Goodnow CC. 1998. Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity 8(4):497-508. [PubMed: 9586639]  [MGI Ref ID J:110531]

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]

Cyster JG; Goodnow CC. 1995. Protein tyrosine phosphatase 1C negatively regulates antigen receptor signaling in B lymphocytes and determines thresholds for negative selection. Immunity 2(1):13-24. [PubMed: 7600299]  [MGI Ref ID J:28348]

Deng C; Minguela A; Hussain RZ; Lovett-Racke AE; Radu C; Ward ES; Racke MK. 2002. Expression of the tyrosine phosphatase SRC homology 2 domain-containing protein tyrosine phosphatase 1 determines T cell activation threshold and severity of experimental autoimmune encephalomyelitis. J Immunol 168(9):4511-8. [PubMed: 11970996]  [MGI Ref ID J:125454]

Deng C; Wu B; Yang H; Hussain RZ; Lovett-Racke AE; Christadoss P; Racke MK. 2003. Decreased expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 reduces T cell activation threshold but not the severity of experimental autoimmune myasthenia gravis. J Neuroimmunol 138(1-2):76-82. [PubMed: 12742656]  [MGI Ref ID J:118963]

Dominique V; Francis L. 1995. Interactions of the scid or beige mutations with the viable motheaten mutation. Autoimmunity 22(4):199-207. [PubMed: 8781712]  [MGI Ref ID J:33985]

Dubois MJ; Bergeron S; Kim HJ; Dombrowski L; Perreault M; Fournes B; Faure R; Olivier M; Beauchemin N; Shulman GI; Siminovitch KA; Kim JK; Marette A. 2006. The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis. Nat Med 12(5):549-56. [PubMed: 16617349]  [MGI Ref ID J:109558]

Forget G; Siminovitch KA; Brochu S; Rivest S; Radzioch D; Olivier M. 2001. Role of host phosphotyrosine phosphatase SHP-1 in the development of murine leishmaniasis. Eur J Immunol 31(11):3185-96. [PubMed: 11745335]  [MGI Ref ID J:72585]

Froidevaux S; Kuntz L; Velin D; Loor F. 1991. Different nature of the proliferation defects of GLD, LPR and MEV C57BL/6 mouse lymphoid cells. Autoimmunity 10(3):233-40. [PubMed: 1756226]  [MGI Ref ID J:1661]

Gross AJ; Lyandres JR; Panigrahi AK; Prak ET; DeFranco AL. 2009. Developmental acquisition of the Lyn-CD22-SHP-1 inhibitory pathway promotes B cell tolerance. J Immunol 182(9):5382-92. [PubMed: 19380785]  [MGI Ref ID J:150309]

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]

Hayashi S; Tsuneto M; Yamada T; Nose M; Yoshino M; Shultz LD; Yamazaki H. 2004. Lipopolysaccharide-induced osteoclastogenesis in Src homology 2-domain phosphatase-1-deficient viable motheaten mice. Endocrinology 145(6):2721-9. [PubMed: 14988381]  [MGI Ref ID J:105632]

Hayes SM; Shultz LD; Greiner DL. 1994. Localization of prothymocytes from wild-type and viable motheaten mice following intravenous injection into irradiated adoptive recipients. Cell Immunol 153(2):344-55. [PubMed: 8118868]  [MGI Ref ID J:16613]

Ho LH; Uehara T; Chen CC; Kubagawa H; Cooper MD. 1999. Constitutive tyrosine phosphorylation of the inhibitory paired Ig-like receptor PIR-B. Proc Natl Acad Sci U S A 96(26):15086-90. [PubMed: 10611342]  [MGI Ref ID J:119839]

Horvat A; Schwaiger F; Hager G; Brocker F; Streif R; Knyazev P; Ullrich A; Kreutzberg GW. 2001. A novel role for protein tyrosine phosphatase shp1 in controlling glial activation in the normal and injured nervous system. J Neurosci 21(3):865-74. [PubMed: 11157073]  [MGI Ref ID J:109385]

Huang Z; Xin J; Coleman J; Huang H. 2005. IFN-gamma suppresses STAT6 phosphorylation by inhibiting its recruitment to the IL-4 receptor. J Immunol 174(3):1332-7. [PubMed: 15661890]  [MGI Ref ID J:96417]

Jang MK; Kim SH; Lee KY; Kim TB; Moon KA; Park CS; Bae YJ; Zhu Z; Moon HB; Cho YS. 2010. The tyrosine phosphatase, SHP-1, is involved in bronchial mucin production during oxidative stress. Biochem Biophys Res Commun 393(1):137-43. [PubMed: 20117097]  [MGI Ref ID J:158013]

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]

Joliat MJ; Lang PA; Lyons BL; Burzenski L; Lynes MA; Yi T; Sundberg JP; Shultz LD. 2002. Absence of CD5 Dramatically Reduces Progression of Pulmonary Inflammatory Lesions in SHP-1 Protein-Tyrosine Phosphatase-Deficient 'Viable Motheaten' Mice. J Autoimmun 18(2):105-17. [PubMed: 11908943]  [MGI Ref ID J:76141]

Keilhack H; Muller M; Bohmer SA; Frank C; Weidner KM; Birchmeier W; Ligensa T; Berndt A; Kosmehl H; Gunther B; Muller T; Birchmeier C; Bohmer FD. 2001. Negative Regulation of Ros Receptor Tyrosine Kinase Signaling. An epithelial function of the sh2 domain protein tyrosine phosphatase shp-1. J Cell Biol 152(2):325-34. [PubMed: 11266449]  [MGI Ref ID J:67582]

Khaled AR; Butfiloski EJ; Sobel ES; Schiffenbauer J. 1998. Functional consequences of the SHP-1 defect in motheaten viable mice: role of NF-kappa B. Cell Immunol 185(1):49-58. [PubMed: 9636682]  [MGI Ref ID J:48053]

Khaled AR; Butfiloski EJ; Villas B; Sobel ES; Schiffenbauer J. 1999. Aberrant expression of the NF-kappaB and IkappaB proteins in B cells from viable motheaten mice. Autoimmunity 30(2):115-28. [PubMed: 10435725]  [MGI Ref ID J:117314]

Kim CH; Qu CK; Hangoc G; Cooper S; Anzai N; Feng GS; Broxmeyer HE. 1999. Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses. J Exp Med 190(5):681-90. [PubMed: 10477552]  [MGI Ref ID J:57611]

Kim HJ; Zhang K; Zhang L; Ross FP; Teitelbaum SL; Faccio R. 2009. The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo. Proc Natl Acad Sci U S A 106(7):2325-30. [PubMed: 19171907]  [MGI Ref ID J:146296]

Kovarik J; Kuntz L; Ryffel B; Borel JF. 1994. The viable motheaten (mev) mouse--a new model for arthritis. J Autoimmun 7(5):575-88. [PubMed: 7840851]  [MGI Ref ID J:20845]

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]

Lee S; Muniyappa R; Yan X; Chen H; Yue LQ; Hong EG; Kim JK; Quon MJ. 2008. Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice. Am J Physiol Endocrinol Metab 294(2):E261-70. [PubMed: 18003716]  [MGI Ref ID J:133294]

Liang B; Workman C; Lee J; Chew C; Dale BM; Colonna L; Flores M; Li N; Schweighoffer E; Greenberg S; Tybulewicz V; Vignali D; Clynes R. 2008. Regulatory T Cells Inhibit Dendritic Cells by Lymphocyte Activation Gene-3 Engagement of MHC Class II. J Immunol 180(9):5916-26. [PubMed: 18424711]  [MGI Ref ID J:134316]

Lipsanen V; Walter B; Emara M; Siminovitch K; Lam J; Kaushik A. 1997. Restricted CDR3 length of the heavy chain is characteristic of six randomly isolated disease-associated VH J558+ IgM autoantibodies in lupus prone motheaten mice. Int Immunol 9(5):655-64. [PubMed: 9184911]  [MGI Ref ID J:40959]

Liu SQ; Tefft BJ; Zhang A; Zhang LQ; Wu YH. 2008. Formation of smooth muscle alpha actin filaments in CD34+ bone marrow cells on arterial elastic laminae: potential role of SH2 domain-containing protein tyrosine phosphatase-1. Matrix Biol 27(4):282-94. [PubMed: 18258420]  [MGI Ref ID J:139383]

Lowin-Kropf B; Kunz B; Beermann F; Held W. 2000. Impaired natural killing of MHC class I-deficient targets by NK cells expressing a catalytically inactive form of SHP-1. J Immunol 165(3):1314-21. [PubMed: 10903732]  [MGI Ref ID J:120439]

Lyons BL; Lynes MA; Burzenski L; Joliat MJ; Hadjout N; Shultz LD. 2003. Mechanisms of anemia in SHP-1 protein tyrosine phosphatase-deficient 'viable motheaten' mice. Exp Hematol 31(3):234-43. [PubMed: 12644021]  [MGI Ref ID J:82283]

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]

Ma G; Pan PY; Eisenstein S; Divino CM; Lowell CA; Takai T; Chen SH. 2011. Paired Immunoglobin-like Receptor-B Regulates the Suppressive Function and Fate of Myeloid-Derived Suppressor Cells. Immunity 34(3):385-95. [PubMed: 21376641]  [MGI Ref ID J:170325]

Massa PT; Wu C; Fecenko-Tacka K. 2004. Dysmyelination and reduced myelin basic protein gene expression by oligodendrocytes of SHP-1-deficient mice. J Neurosci Res 77(1):15-25. [PubMed: 15197735]  [MGI Ref ID J:104821]

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]

Nakayama K; Takahashi K; Shultz LD; Miyakawa K; Tomita K. 1997. Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase. Int J Exp Pathol 78(4):245-57. [PubMed: 9505936]  [MGI Ref ID J:43013]

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]

Nishimura H; Strominger JL. 2006. Involvement of a tissue-specific autoantibody in skin disorders of murine systemic lupus erythematosus and autoinflammatory diseases. Proc Natl Acad Sci U S A 103(9):3292-7. [PubMed: 16492738]  [MGI Ref ID J:107174]

Oh SY; Zheng T; Kim YK; Cohn L; Homer RJ; McKenzie AN; Zhu Z. 2009. A critical role of SHP-1 in regulation of type 2 inflammation in the lung. Am J Respir Cell Mol Biol 40(5):568-74. [PubMed: 18952567]  [MGI Ref ID J:160867]

Oldenborg PA; Gresham HD; Lindberg FP. 2001. CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis. J Exp Med 193(7):855-62. [PubMed: 11283158]  [MGI Ref ID J:120547]

Pani G; Fischer KD; Mlinaric-Rascan I; Siminovitch KA. 1996. Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase. J Exp Med 184(3):839-52. [PubMed: 9064344]  [MGI Ref ID J:35279]

Pani G; Siminovitch KA; Paige CJ. 1997. The motheaten mutation rescues B cell signaling and development in CD45-deficient mice. J Exp Med 186(4):581-8. [PubMed: 9254656]  [MGI Ref ID J:42368]

Park IK; Shultz LD; Letterio JJ; Gorham JD. 2005. TGF-beta1 inhibits T-bet induction by IFN-gamma in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1. J Immunol 175(9):5666-74. [PubMed: 16237056]  [MGI Ref ID J:119358]

Park-Min KH; Serbina NV; Yang W; Ma X; Krystal G; Neel BG; Nutt SL; Hu X; Ivashkiv LB. 2007. FcgammaRIII-dependent inhibition of interferon-gamma responses mediates suppressive effects of intravenous immune globulin. Immunity 26(1):67-78. [PubMed: 17239631]  [MGI Ref ID J:118322]

Qu C; Nguyen S; Chen J; Feng GS. 2001. Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development. Blood 97(4):911-4. [PubMed: 11159516]  [MGI Ref ID J:67405]

Ramachandran IR; Song W; Lapteva N; Seethammagari M; Slawin KM; Spencer DM; Levitt JM. 2011. The phosphatase SRC homology region 2 domain-containing phosphatase-1 is an intrinsic central regulator of dendritic cell function. J Immunol 186(7):3934-45. [PubMed: 21357539]  [MGI Ref ID J:170692]

Roach TI; Slater SE; White LS; Zhang X; Majerus PW; Brown EJ; Thomas ML. 1998. The protein tyrosine phosphatase SHP-1 regulates integrin-mediated adhesion of macrophages. Curr Biol 8(18):1035-8. [PubMed: 9740804]  [MGI Ref ID J:95613]

Saitoh Y; Kelsoe G; Bona C; Kaushik A. 1995. Skewed VH and V kappa gene family expression and pairing occurs among B lymphocytes in autoimmune motheaten mice. Autoimmunity 21(3):185-193. [PubMed: 8822276]  [MGI Ref ID J:31222]

Shultz LD; Coman DR; Bailey CL; Beamer WG; Sidman CL. 1984. Viable motheaten, a new allele at the motheaten locus. I. Pathology. Am J Pathol 116(2):179-92. [PubMed: 6380298]  [MGI Ref ID J:7531]

Shultz LD; Coman DR; Lyons BL; Sidman CL; Taylor S. 1987. Development of plasmacytoid cells with Russell bodies in autoimmune viable motheaten mice. Am J Pathol 127(1):38-50. [PubMed: 3551623]  [MGI Ref ID J:14936]

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; Marshall JD; Masiello NC; Roths JB; Shultz LD. 1984. Novel B-cell maturation factor from spontaneously autoimmune viable motheaten mice. Proc Natl Acad Sci U S A 81(22):7199-202. [PubMed: 6334306]  [MGI Ref ID J:7665]

Sidman CL; Shultz LD; Evans R. 1985. A serum-derived molecule from autoimmune viable motheaten mice potentiates the action of a B cell maturation factor. J Immunol 135(2):870-2. [PubMed: 3891855]  [MGI Ref ID J:7905]

Sprecher E; Becker Y; Kraal G; Hall E; Shultz LD. 1990. Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice. Arch Dermatol Res 282(3):188-93. [PubMed: 2196000]  [MGI Ref ID J:116957]

Su X; Zhou T; Wang Z; Yang P; Jope RS; Mountz JD. 1995. Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis. Immunity 2(4):353-62. [PubMed: 7536621]  [MGI Ref ID J:25720]

Su X; Zhou T; Yang PA; Wang Z; Mountz JD. 1996. Hematopoietic cell protein-tyrosine phosphatase-deficient motheaten mice exhibit T cell apoptosis defect. J Immunol 156(11):4198-208. [PubMed: 8666788]  [MGI Ref ID J:110824]

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]

Thrall RS; Vogel SN; Evans R; Shultz LD. 1997. Role of tumor necrosis factor-alpha in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. Am J Pathol 151(5):1303-10. [PubMed: 9358756]  [MGI Ref ID J:43848]

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]

Ulivieri C; Valensin S; Majolini MB; Matthews RJ; Baldari CT. 2003. Normal B-1 cell development but defective BCR signaling in Lck-/- mice. Eur J Immunol 33(2):441-5. [PubMed: 12645942]  [MGI Ref ID J:115705]

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]

Van Zant G; Shultz L. 1989. Hematologic abnormalities of the immunodeficient mouse mutant, viable motheaten (mev). Exp Hematol 17(2):81-7. [PubMed: 2783574]  [MGI Ref ID J:14937]

Volgina VV; Sun T; Bozek G; Martin TE; Storb U. 2007. Scarcity of lambda1 B cells in mice with a single point mutation in Clambda1 is due to a low BCR signal caused by misfolded lambda1 light chain. Mol Immunol 44(6):1417-28. [PubMed: 16860389]  [MGI Ref ID J:113218]

Wasserman HA; Beal CD; Zhang Y; Jiang N; Zhu C; Evavold BD. 2008. MHC variant peptide-mediated anergy of encephalitogenic T cells requires SHP-1. J Immunol 181(10):6843-9. [PubMed: 18981103]  [MGI Ref ID J:140946]

Wei G; Guo J; Doseff AI; Kusewitt DF; Man AK; Oshima RG; Ostrowski MC. 2004. Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model. J Immunol 173(2):1374-9. [PubMed: 15240733]  [MGI Ref ID J:91944]

Westhoff CM; Whittier A; Kathol S; McHugh J; Zajicek C; Shultz LD ; Wylie DE. 1997. DNA-binding antibodies from viable motheaten mutant mice: implications for B cell tolerance. J Immunol 159(6):3024-33. [PubMed: 9300728]  [MGI Ref ID J:42564]

Xiao W; Ando T; Wang HY; Kawakami Y; Kawakami T. 2010. Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease. Blood 116(26):6003-13. [PubMed: 20858858]  [MGI Ref ID J:167395]

Xiao W; Hong H; Kawakami Y; Kato Y; Wu D; Yasudo H; Kimura A; Kubagawa H; Bertoli LF; Davis RS; Chau LA; Madrenas J; Hsia CC; Xenocostas A; Kipps TJ; Hennighausen L; Iwama A; Nakauchi H; Kawakami T. 2009. Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5. Cancer Cell 16(2):161-71. [PubMed: 19647226]  [MGI Ref ID J:151972]

Xiao W; Kashiwakura J; Hong H; Yasudo H; Ando T; Maeda-Yamamoto M; Wu D; Kawakami Y; Kawakami T. 2011. Phospholipase C-beta3 Regulates FcvarepsilonRI-Mediated Mast Cell Activation by Recruiting the Protein Phosphatase SHP-1. Immunity 34(6):893-904. [PubMed: 21683628]  [MGI Ref ID J:174006]

Yamada G; Nakamura S; Haraguchi R; Sakai M; Suzuki K; Miyado K; Hasuwa H; Ogino Y; Minami T; Tohno Y; Blum M; Shultz LD. 1998. Aberrant regulation of bone trace elements in motheaten and osteopetrosis mutant mice. Cell Mol Biol (Noisy-le-grand) 44(2):315-9. [PubMed: 9593582]  [MGI Ref ID J:47798]

Yu WM; Wang S; Keegan AD; Williams MS; Qu CK. 2005. Abnormal Th1 cell differentiation and IFN-gamma production in T lymphocytes from motheaten viable mice mutant for Src homology 2 domain-containing protein tyrosine phosphatase-1. J Immunol 174(2):1013-9. [PubMed: 15634925]  [MGI Ref ID J:95832]

Zhang H; Meng F; Chu CL; Takai T; Lowell CA. 2005. The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B. Immunity 22(2):235-46. [PubMed: 15723811]  [MGI Ref ID J:96676]

Zhang J; Somani AK; Watt S; Mills GB; Siminovitch KA. 1999. The Src-homology domain 2-bearing protein tyrosine phosphatase-1 inhibits antigen receptor-induced apoptosis of activated peripheral T cells. J Immunol 162(11):6359-67. [PubMed: 10352248]  [MGI Ref ID J:55030]

Zhang J; Somani AK; Yuen D; Yang Y; Love PE; Siminovitch KA. 1999. Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection. J Immunol 163(6):3012-21. [PubMed: 10477564]  [MGI Ref ID J:118908]

Zhang L; Oh SY; Wu X; Oh MH; Wu F; Schroeder JT; Takemoto CM; Zheng T; Zhu Z. 2010. SHP-1 deficient mast cells are hyperresponsive to stimulation and critical in initiating allergic inflammation in the lung. J Immunol 184(3):1180-90. [PubMed: 20042576]  [MGI Ref ID J:159529]

Zhou D; Collins CA; Wu P; Brown EJ. 2010. Protein tyrosine phosphatase SHP-1 positively regulates TLR-induced IL-12p40 production in macrophages through inhibition of phosphatidylinositol 3-kinase. J Leukoc Biol 87(5):845-55. [PubMed: 20145200]  [MGI Ref ID J:160352]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Mating System	Heterozygote x Heterozygote         (Female x Male)   29-SEP-09
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Mouse Mutant Resource collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

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

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.

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.