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. 1996 Feb 1;183(2):371–380. doi: 10.1084/jem.183.2.371

B and T cells are not required for the viable motheaten phenotype

PMCID: PMC2192436  PMID: 8627150

Abstract

Hematopoietic cell phosphatase (HCP), encoded by the hcph gene, (also called PTP1C, SHP, SH-PTP1, and PTPN6) is deficient in motheaten (me/me), and the allelic viable motheaten (me(v)/me(v)) mice. Since HCP is expressed in many cell types and protein phosphorylation is a major mechanism of regulating protein function, it is not surprising that the motheaten phenotype is pleiotropic. It is commonly thought that immune system involvement causes this disease. If so, the motheaten disease ought to be alleviated when the recombination activation gene-1 (RAG-1) is disrupted because there will be no V(D)J rearrangement and thus impaired development of B and T cells. We bred homozygous, double- mutant me(v)/me(v) x RAG 1 -/- mice and found that, in fact, inflamed paws, and splenomegaly with elevated myelopoiesis. Thus, except for autoantibodies, the motheaten phenotype does not depend on the presence of B and T cells. This observation cautions the use of motheaten mice as a model of autoimmune disease.

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Selected References

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  1. Ault K. A., Springer T. A. Cross-reaction of a rat-anti-mouse phagocyte-specific monoclonal antibody (anti-Mac-1) with human monocytes and natural killer cells. J Immunol. 1981 Jan;126(1):359–364. [PubMed] [Google Scholar]
  2. De Sousa M. A., Parrott D. M., Pantelouris E. M. The lymphoid tissues in mice with congenital aplasia of the thymus. Clin Exp Immunol. 1969 Jun;4(6):637–644. [PMC free article] [PubMed] [Google Scholar]
  3. Fulop G. M., Phillips R. A. The scid mutation in mice causes a general defect in DNA repair. Nature. 1990 Oct 4;347(6292):479–482. doi: 10.1038/347479a0. [DOI] [PubMed] [Google Scholar]
  4. Green M. C., Shultz L. D. Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J Hered. 1975 Sep-Oct;66(5):250–258. doi: 10.1093/oxfordjournals.jhered.a108625. [DOI] [PubMed] [Google Scholar]
  5. Hendrickson E. A., Qin X. Q., Bump E. A., Schatz D. G., Oettinger M., Weaver D. T. A link between double-strand break-related repair and V(D)J recombination: the scid mutation. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4061–4065. doi: 10.1073/pnas.88.10.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kindred B. Nude mice in immunology. Prog Allergy. 1979;26:137–238. [PubMed] [Google Scholar]
  7. Koo G. C., Manyak C. L., Dasch J., Ellingsworth L., Shultz L. D. Suppressive effects of monocytic cells and transforming growth factor-beta on natural killer cell differentiation in autoimmune viable motheaten mutant mice. J Immunol. 1991 Aug 15;147(4):1194–1200. [PubMed] [Google Scholar]
  8. Koo G. C., Rosen H., Sirotina A., Ma X. D., Shultz L. D. Anti-CD11b antibody prevents immunopathologic changes in viable moth-eaten bone marrow chimeric mice. J Immunol. 1993 Dec 15;151(12):6733–6741. [PubMed] [Google Scholar]
  9. Kozlowski M., Mlinaric-Rascan I., Feng G. S., Shen R., Pawson T., Siminovitch K. A. Expression and catalytic activity of the tyrosine phosphatase PTP1C is severely impaired in motheaten and viable motheaten mice. J Exp Med. 1993 Dec 1;178(6):2157–2163. doi: 10.1084/jem.178.6.2157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Matthews R. J., Bowne D. B., Flores E., Thomas M. L. Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol Cell Biol. 1992 May;12(5):2396–2405. doi: 10.1128/mcb.12.5.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mombaerts P., Iacomini J., Johnson R. S., Herrup K., Tonegawa S., Papaioannou V. E. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992 Mar 6;68(5):869–877. doi: 10.1016/0092-8674(92)90030-g. [DOI] [PubMed] [Google Scholar]
  12. Plutzky J., Neel B. G., Rosenberg R. D., Eddy R. L., Byers M. G., Jani-Sait S., Shows T. B. Chromosomal localization of an SH2-containing tyrosine phosphatase (PTPN6). Genomics. 1992 Jul;13(3):869–872. doi: 10.1016/0888-7543(92)90172-o. [DOI] [PubMed] [Google Scholar]
  13. Plutzky J., Neel B. G., Rosenberg R. D. Isolation of a src homology 2-containing tyrosine phosphatase. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1123–1127. doi: 10.1073/pnas.89.3.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Scher I. The CBA/N mouse strain: an experimental model illustrating the influence of the X-chromosome on immunity. Adv Immunol. 1982;33:1–71. doi: 10.1016/s0065-2776(08)60834-2. [DOI] [PubMed] [Google Scholar]
  15. Scribner C. L., Hansen C. T., Klinman D. M., Steinberg A. D. The interaction of the xid and me genes. J Immunol. 1987 Jun 1;138(11):3611–3617. [PubMed] [Google Scholar]
  16. Shen S. H., Bastien L., Posner B. I., Chrétien P. A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature. 1991 Aug 22;352(6337):736–739. doi: 10.1038/352736a0. [DOI] [PubMed] [Google Scholar]
  17. Shultz L. D., Coman D. R., Bailey C. L., Beamer W. G., Sidman C. L. "Viable motheaten," a new allele at the motheaten locus. I. Pathology. Am J Pathol. 1984 Aug;116(2):179–192. [PMC free article] [PubMed] [Google Scholar]
  18. Shultz L. D., Green M. C. Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins. J Immunol. 1976 Apr;116(4):936–943. [PubMed] [Google Scholar]
  19. Shultz L. D. Pleiotropic effects of deleterious alleles at the "motheaten" locus. Curr Top Microbiol Immunol. 1988;137:216–222. doi: 10.1007/978-3-642-50059-6_32. [DOI] [PubMed] [Google Scholar]
  20. Shultz L. D., Schweitzer P. A., Rajan T. V., Yi T., Ihle J. N., Matthews R. J., Thomas M. L., Beier D. R. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell. 1993 Jul 2;73(7):1445–1454. doi: 10.1016/0092-8674(93)90369-2. [DOI] [PubMed] [Google Scholar]
  21. Shultz L. D., Sidman C. L. Genetically determined murine models of immunodeficiency. Annu Rev Immunol. 1987;5:367–403. doi: 10.1146/annurev.iy.05.040187.002055. [DOI] [PubMed] [Google Scholar]
  22. Sidman C. L., Shultz L. D., Hardy R. R., Hayakawa K., Herzenberg L. A. Production of immunoglobulin isotypes by Ly-1+ B cells in viable motheaten and normal mice. Science. 1986 Jun 13;232(4756):1423–1425. doi: 10.1126/science.3487115. [DOI] [PubMed] [Google Scholar]
  23. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  24. Tsui H. W., Siminovitch K. A., de Souza L., Tsui F. W. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet. 1993 Jun;4(2):124–129. doi: 10.1038/ng0693-124. [DOI] [PubMed] [Google Scholar]
  25. Wicker L. S., Scher I. X-linked immune deficiency (xid) of CBA/N mice. Curr Top Microbiol Immunol. 1986;124:87–101. doi: 10.1007/978-3-642-70986-9_6. [DOI] [PubMed] [Google Scholar]
  26. Yi T. L., Cleveland J. L., Ihle J. N. Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. Mol Cell Biol. 1992 Feb;12(2):836–846. doi: 10.1128/mcb.12.2.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yi T., Gilbert D. J., Jenkins N. A., Copeland N. G., Ihle J. N. Assignment of a novel protein tyrosine phosphatase gene (Hcph) to mouse chromosome 6. Genomics. 1992 Nov;14(3):793–795. doi: 10.1016/s0888-7543(05)80189-2. [DOI] [PubMed] [Google Scholar]

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