Abstract
Scurfy (sf) is a spontaneous, sex-linked, recessive mutation that maps to the extreme proximal portion of the X chromosome, about 2 centimorgans from sparse fur (spf). Hemizygotes for sf manifest several clinical disorders, evident at 14 days of age, including scaliness and crusting of the eyelids, ears, and tail, runting, reddening and swelling of the genital papilla, anemia, cachexia, and early death (average, 24 days). Our studies indicate that the phenotype of hemizygous scurfy is not, as has been suggested, a model for human X-linked ichthyosis, but appears to be a disease primarily affecting the lymphoreticular, and possibly the hematopoietic, systems. Gross lesions include marked splenomegaly, hepatomegaly, enlarged lymph nodes, and variable thickening of the ears. The characteristic histologic lesion is a lymphohistiocytic proliferation and infiltration of peripheral lymph nodes, spleen, liver, and skin. In routine hematoxylin and eosin-stained sections, these lesions efface lymph node architecture, thicken the dermis, and form nodular portal infiltrates in the liver. Scurfy lesions characteristically contain a population of large blastlike cells with round to oval nuclei, a vesicular chromatin pattern, and prominent single nucleoli. Mixed perivascular infiltrates of lymphocytes, macrophages, and granulocytes sometimes are found in kidney, heart, pancreas, lung, and mesenteries. There is excessive hematopoiesis in the liver and spleen. Cells expressing B220 or Thy-1 antigens localize to appropriate areas in the lymph nodes and spleen, but are rare in the portal infiltrates and are absent from the skin. There is a marked, polyclonal increase in serum IgG, severe Coombs'-positive anemia, and leukocytosis with atypical mononuclear cells. Scurfy mice are negative for antinuclear antibodies. Despite their morphologically aberrant lymphoreticular system, scurfy mice can exist in a conventional environment without evidence of opportunistic infection. Raising scurfy mice in a specific-pathogen-free environment does not alter disease expression. Thus, while our findings indicate that scurfy disease may be the result of immune dysfunction, it is not a classic immunodeficiency.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Lyon M. F. The William Allan memorial award address: X-chromosome inactivation and the location and expression of X-linked genes. Am J Hum Genet. 1988 Jan;42(1):8–16. [PMC free article] [PubMed] [Google Scholar]
- Oliff A., Defeo-Jones D., Boyer M., Martinez D., Kiefer D., Vuocolo G., Wolfe A., Socher S. H. Tumors secreting human TNF/cachectin induce cachexia in mice. Cell. 1987 Aug 14;50(4):555–563. doi: 10.1016/0092-8674(87)90028-6. [DOI] [PubMed] [Google Scholar]
- Russell W. L., Russell L. B., Gower J. S. EXCEPTIONAL INHERITANCE OF A SEX-LINKED GENE IN THE MOUSE EXPLAINED ON THE BASIS THAT THE X/O SEX-CHROMOSOME CONSTITUTION IS FEMALE. Proc Natl Acad Sci U S A. 1959 Apr;45(4):554–560. doi: 10.1073/pnas.45.4.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sharpe R. J., Margolis R. J., Askari M., Amento E. P., Granstein R. D. Induction of dermal and subcutaneous inflammation by recombinant cachectin/tumor necrosis factor (TNF alpha) in the mouse. J Invest Dermatol. 1988 Oct;91(4):353–357. doi: 10.1111/1523-1747.ep12475754. [DOI] [PubMed] [Google Scholar]
- Talmadge J. E., Phillips H., Schneider M., Rowe T., Pennington R., Bowersox O., Lenz B. Immunomodulatory properties of recombinant murine and human tumor necrosis factor. Cancer Res. 1988 Feb 1;48(3):544–550. [PubMed] [Google Scholar]
- Webster D., France J. T., Shapiro L. J., Weiss R. X-linked ichthyosis due to steroid-sulphatase deficiency. Lancet. 1978 Jan 14;1(8055):70–72. doi: 10.1016/s0140-6736(78)90005-3. [DOI] [PubMed] [Google Scholar]
- Welshons W. J., Russell L. B. THE Y-CHROMOSOME AS THE BEARER OF MALE DETERMINING FACTORS IN THE MOUSE. Proc Natl Acad Sci U S A. 1959 Apr;45(4):560–566. doi: 10.1073/pnas.45.4.560. [DOI] [PMC free article] [PubMed] [Google Scholar]