Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. Feb 1, 1996; 183(2): 371–380.
PMCID: PMC2192436

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

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.

Full Text

The Full Text of this article is available as a PDF (2.5M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Yi T, Gilbert DJ, Jenkins NA, Copeland NG, Ihle JN. Assignment of a novel protein tyrosine phosphatase gene (Hcph) to mouse chromosome 6. Genomics. 1992 Nov;14(3):793–795. [PubMed]
  • Shen SH, Bastien L, Posner BI, 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. [PubMed]
  • Matthews RJ, Bowne DB, Flores E, Thomas ML. 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. [PMC free article] [PubMed]
  • Plutzky J, Neel BG, Rosenberg RD. Isolation of a src homology 2-containing tyrosine phosphatase. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1123–1127. [PMC free article] [PubMed]
  • Plutzky J, Neel BG, Rosenberg RD, Eddy RL, Byers MG, Jani-Sait S, Shows TB. Chromosomal localization of an SH2-containing tyrosine phosphatase (PTPN6). Genomics. 1992 Jul;13(3):869–872. [PubMed]
  • Tsui HW, Siminovitch KA, de Souza L, Tsui FW. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet. 1993 Jun;4(2):124–129. [PubMed]
  • Shultz LD, Schweitzer PA, Rajan TV, Yi T, Ihle JN, Matthews RJ, Thomas ML, Beier DR. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell. 1993 Jul 2;73(7):1445–1454. [PubMed]
  • Kozlowski M, Mlinaric-Rascan I, Feng GS, Shen R, Pawson T, Siminovitch KA. 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. [PMC free article] [PubMed]
  • Green MC, Shultz LD. Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J Hered. 1975 Sep-Oct;66(5):250–258. [PubMed]
  • Shultz LD, Coman DR, Bailey CL, Beamer WG, Sidman CL. "Viable motheaten," a new allele at the motheaten locus. I. Pathology. Am J Pathol. 1984 Aug;116(2):179–192. [PMC free article] [PubMed]
  • Koo GC, Rosen H, Sirotina A, Ma XD, Shultz LD. Anti-CD11b antibody prevents immunopathologic changes in viable moth-eaten bone marrow chimeric mice. J Immunol. 1993 Dec 15;151(12):6733–6741. [PubMed]
  • Shultz LD, Green MC. Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins. J Immunol. 1976 Apr;116(4):936–943. [PubMed]
  • Sidman CL, Shultz LD, Hardy RR, Hayakawa K, Herzenberg LA. Production of immunoglobulin isotypes by Ly-1+ B cells in viable motheaten and normal mice. Science. 1986 Jun 13;232(4756):1423–1425. [PubMed]
  • Shultz LD. Pleiotropic effects of deleterious alleles at the "motheaten" locus. Curr Top Microbiol Immunol. 1988;137:216–222. [PubMed]
  • Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992 Mar 6;68(5):869–877. [PubMed]
  • Shultz LD, Sidman CL. Genetically determined murine models of immunodeficiency. Annu Rev Immunol. 1987;5:367–403. [PubMed]
  • Fulop GM, Phillips RA. The scid mutation in mice causes a general defect in DNA repair. Nature. 1990 Oct 4;347(6292):479–482. [PubMed]
  • Hendrickson EA, Qin XQ, Bump EA, Schatz DG, Oettinger M, Weaver DT. 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. [PMC free article] [PubMed]
  • Scribner CL, Hansen CT, Klinman DM, Steinberg AD. The interaction of the xid and me genes. J Immunol. 1987 Jun 1;138(11):3611–3617. [PubMed]
  • De Sousa MA, Parrott DM, Pantelouris EM. The lymphoid tissues in mice with congenital aplasia of the thymus. Clin Exp Immunol. 1969 Jun;4(6):637–644. [PMC free article] [PubMed]
  • Kindred B. Nude mice in immunology. Prog Allergy. 1979;26:137–238. [PubMed]
  • 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. [PubMed]
  • Wicker LS, Scher I. X-linked immune deficiency (xid) of CBA/N mice. Curr Top Microbiol Immunol. 1986;124:87–101. [PubMed]
  • Springer T, Galfré G, Secher DS, Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. [PubMed]
  • Ault KA, Springer TA. 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]
  • Koo GC, Manyak CL, Dasch J, Ellingsworth L, Shultz LD. 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]
  • Yi TL, Cleveland JL, Ihle JN. 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. [PMC free article] [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...