Expression of enhanced spontaneous and γ-ray-induced apoptosis by lymphocytes of the wasted mouse

Gayle E Woloschak*, Chin Mei Chang-Liu, Jen Chung, C. R. Libertin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including increased sensitivity of lymphocytes to ionizing radiation, neurologic dysfunction, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes. Past work has documented an inability to establish cultured T cell lines, an abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in the wst/wst mouse relative to controls. The experiments reported here were designed to examine splenic and thymic lymphocytes from the wasted and control mouse for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (which has been associated with apoptosis) in thymic lymphocytes and to a lesser extent in spinal cord in the wst/wst mouse relative to controls; expression of Rp-2 and Tcl-30 mRNA (also reported to be induced during apoptosis) were not detectable in spleen or thymus. Expression of Rp-2, Rp-8, and Tcl-30 mRNA in other affected tissues of the wasted mouse (brain and liver) were similar in the wasted mouse and controls. Thymus and spleen from the wasted mouse have reduced numbers of viable cells relative to controls. Higher spontaneous DNA fragmentation was observed in lymphocytes from the wasted mouse than in controls; however, γ-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in lymphocytes derived from the wasted mouse relative to controls. These results suggest that high spontaneous and γ-ray-induced apoptosis in T cells of the wasted mouse may contribute to the mechanism underlying the observed lymphocyte and DNA repair abnormalities.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalInternational Journal of Radiation Biology
Volume69
Issue number1
DOIs
StatePublished - Mar 6 1996

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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