Article | Published:

Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene

Nature Genetics volume 4, pages 124129 (1993) | Download Citation

Subjects

Abstract

Mice with the recessive motheaten (me) or the allelic viable motheaten (mev) mutations express a severe autoimmune and immunodeficiency syndrome. We have shown that the basic defect in these mice involves lesions in the gene which encodes haematopoietic cell phosphatase (HCP). These mice thus provide excellent models for investigating the roles of phosphatases in haematopoiesis and the nature of the genetic and cellular events linking impaired haematopoiesis to severe immunodeficiency and expression of systemic autoimmunity.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , Motheaten, an immunodeficient mutant of the mouse. J. Hered. 66, 250–258 (1975).

  2. 2.

    , & The mouse mutant “motheaten”. I. Development of lymphocyte populations. J. Immunol. 121, 2392–2398 (1978).

  3. 3.

    , , , & Viable Motheaten”, a new allele at the Motheaten locus. I. Pathology. Am. J. Pathol. 116, 179–192 (1984).

  4. 4.

    et al. Defective lymphopoiesis in the bone marrow of motheaten (me/me) and viable motheaten (mev/mev) mutant mice. I. Analysis of the development of prothymocytes, B lineage cells and terminal deoxynucleotidyl-transferase-positive cells. J. exp. Med. 164, 1129–1144 (1986).

  5. 5.

    , , & Phenotypic and functional effects of the motheaten gene on murine B and T lymphocytes. J. Immunol. 122, 884–891 (1979).

  6. 6.

    , & The mouse mutant “motheaten. II. Functional studies of the immune system. J. Immunol. 121, 2399–2404 (1978).

  7. 7.

    , , , & Production of immunoglobulin isotypes by Ly–1+ B cells in viable motheaten and normal mice. Science 232, 1423–1425 (1986).

  8. 8.

    , & Mutations in mice that influence natural killer (NK) cell activity. Immunogenet. 12, 601–613 (1981).

  9. 9.

    , , , & Suppressive effects of monocytic cells and TGF–beta on NK differentiation in autoimmune viable motheaten mutant mice. J. Immunol. 147, 1194–1200 (1991).

  10. 10.

    , & Spontaneous production of colony-stimulating activity by splenic MAC–1 antigen-positive cells from autoimmune motheaten mice. J. Immunol. 132, 272–276 (1984).

  11. 11.

    , , & Lymphohemopoiesis in culture is prevented by interaction with adherent bone marrow cells from mutant viable motheaten mice. J. Immunol. 140, 2139–2147 (1988).

  12. 12.

    , & Protein tyrosine phosphatase containing SH2 domains. Characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12–p13. Molec. cell Biol. 12, 836–846 (1992).

  13. 13.

    et al. Chromosomal localization of an SH2-containing tyrosine phosphatase (PTPN6). Genomics 13, 869–872 (1992).

  14. 14.

    , , & A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature 352, 736–739 (1991).

  15. 15.

    , , & 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. Molec. cell Biol. 12, 2396–2405 (1992).

  16. 16.

    , & Isolation of an src homology 2-containing tyrosine phosphatase. Proc. natn. Acad. Sci. U.S.A. 89, 1123–1127 (1992).

  17. 17.

    , & Murine “viable motheaten” mutation reveals a gene critical to the development of both B and T lymphocytes. Proc. natn. Acad. Sci. U.S.A. 86, 6279–6282 (1989).

  18. 18.

    A catalogue of splice junction sequences. Nucl. Acid Res. 10, 459–472 (1982).

  19. 19.

    The New Genetics and Clinical Practice 2nd edn 80–81 (University Press, Oxford, 1985).

  20. 20.

    , , , & Assignment of a novel protein tyrosine phosphatase gene (Hcph). Genomics 14, 793–795 (1992).

  21. 21.

    Protein-tyrosine phosphatase: the other side of the coin. Cell 58, 1013–1016 (1989).

  22. 22.

    & Growth factor receptor tyrosine kinases. Ann. Rev. Biochem. 57, 443–478 (1988).

  23. 23.

    & Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. Trends Genet. 6, 350–356 (1990).

  24. 24.

    , , & Expression of a human T-cell protein-tyrosine-phosphatase in baby hamster kidney cells. Proc. natn. Acad. Sci. U.S.A. 87, 7280–7284 (1990).

  25. 25.

    , & Overexpression of a synthetic phospho-tyrosine protein phosphatase gene inhibits normal and transformed cell growth. Int. J. Cancer 51, 652–656 (1992).

  26. 26.

    , , & Effect of protein tyrosine phosphatase 1B expression on transformation by the human neu oncogene. Cancer Res. 52, 478–482 (1992).

  27. 27.

    , , , & SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252, 668–674 (1991).

  28. 28.

    , , & Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18, 5294–5299 (1979).

  29. 29.

    & Single-step method of RNA isolation by acid guanidinum thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156–159 (1987).

  30. 30.

    , & in Molecular Cloning: A Laboratory Manual 2nd edn (Cold Spring Harbor Laboratory Press, New York, 1989).

  31. 31.

    An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide. Nucl. Acid Res. 17, 1266 (1989).

Download references

Author information

Affiliations

  1. The Toronto Hospital, Western Division, Mc14–417, 399 Bathurst Street, Toronto, Ontario, M5T2S8, Canada

    • Hing Wo Tsui
    • , Loretta de Souza
    •  & Florence W.L. Tsui
  2. Departments of Medicine and Immunology, University of Toronto, and the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

    • Katherine A. Siminovitch
    •  & Florence W.L. Tsui
  3. Molecular and Medical Genetics, University of Toronto, and the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

    • Katherine A. Siminovitch

Authors

  1. Search for Hing Wo Tsui in:

  2. Search for Katherine A. Siminovitch in:

  3. Search for Loretta de Souza in:

  4. Search for Florence W.L. Tsui in:

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng0693-124

Further reading