Description

Strain Information

Former Names C57BL/6J-Hcphme/J    (Changed: 16-JUN-05 ) Type Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N20+ (19-FEB-02)

Appearance
black, patchy fur and pigment
Related Genotype: a/a Ptpn6^me/Ptpn6^me

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

Description
Mice homozygous for the motheaten spontaneous mutation (Ptpn6^me) 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, 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 a autoimmune pneumonitis.

Control Information

	Control
	Untested littermates from the colony
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   Ptpn6^me allele

000225

C3FeLe.B6 a/a-Ptpn6me/J

View Strains carrying   Ptpn6^me     (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

      assigned by genotype

Ptpn6^me/Ptpn6^me

        C57BL/6J-Ptpn6^me/J

• skin/coat/nails phenotype
• abnormal coat appearance (MGI Ref ID J:5579)
  • patchy absence of hair as the coat appears gives mice a motheaten appearance
• patchy hair (MGI Ref ID J:5579)
• abnormal skin pigmentation (MGI Ref ID J:5579)
  • recognized at 3 to 4 days of age by patchy absence of skin pigment
• skin lesions (MGI Ref ID J:5579)
  • rapidly progressing lesions develop on the feet by 3 weeks of age
  • as early as 2 days after birth abscesses appear on the skin, rupture and begin to heal in 24 hrs
• pigmentation phenotype
• abnormal skin pigmentation (MGI Ref ID J:5579)
  • recognized at 3 to 4 days of age by patchy absence of skin pigment
• immune system phenotype
• abnormal Peyer's patch morphology (MGI Ref ID J:5579)
  • rarely any differentiation of lymphoid tissue into nodules is found
  • lymphocytes are larger and sparsely distributed
• abnormal humoral immune response (MGI Ref ID J:5579)
  • mice are deficient in capacity for immune response
• increased immunoglobulin level (MGI Ref ID J:5579)
• increased IgA level (MGI Ref ID J:5579)
  • serum levels are elevated
• increased IgG level (MGI Ref ID J:5579)
  • serum levels are elevated
• increased IgM level (MGI Ref ID J:5579)
  • serum levels are markedly elevated above normal
• abnormal immune system cell morphology (MGI Ref ID J:5579)
  • mice have a population of unusual binucleate lymphocytes
• abnormal granulocyte morphology (MGI Ref ID J:5579)
  • differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population
• 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 (MGI Ref ID J:5579)
  • although smaller than normal, the thymus is histologically normal until 25 days of age
  • severe involution and necrosis is found in sick mice, with severity correlating with degree of illness
• enlarged spleen (MGI Ref ID J:5579)
• life span-post-weaning/aging
• premature death (MGI Ref ID J:5579)
  • mortality is high from birth onward with none surviving longer than 8 weeks
• hematopoietic system phenotype
• abnormal granulocyte morphology (MGI Ref ID J:5579)
  • differential counts of blood from 1 to 3 day old mice showed an immature granuloctye population
• 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 (MGI Ref ID J:5579)
  • although smaller than normal, the thymus is histologically normal until 25 days of age
  • severe involution and necrosis is found in sick mice, with severity correlating with degree of illness
• enlarged spleen (MGI Ref ID J:5579)
• respiratory system phenotype
• abnormal lung morphology (MGI Ref ID J:5579)
  • mice develop lesions in the lung by 3 days of age
• cellular phenotype
• decreased apoptosis (MGI Ref ID J:66843)
  • 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.
  • 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
• decreased cellular sensitivity to gamma-irradiation (MGI Ref ID J:66843)
  • the LD50 for homozygous spleen cells is 24.5 Gy gamma radiation versus 6.5 Gy for wildtype splenocytes

View Research Applications

Research Applications

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

Ptpn6^me related

Apoptosis Research

Dermatology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Thyroid Defects

Immunology and Inflammation Research
Autoimmunity
Immunodeficiency
Inflammation

Internal/Organ Research
Lymphoid Tissue Defects
Spleen Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ptpn6me
Allele Name		motheaten
Allele Type		Spontaneous
Common Name(s)		me;
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; SH-PTP1; SHP-1; SHP-1L; SHP1; 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

Ptpn6^me, REST, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

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]

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]

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]

Ptpn6^me related

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]

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]

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]

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]

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]

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]

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; 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]

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]

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. . 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; 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

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply	Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.
Supply Notes	Individual mice are not available for sale. This strain can only be sold as a pair.

Control Information

	Control
	Untested littermates from the colony
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

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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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