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Expression of the Q5k gene was examined by northern blot analysis and polymerase chain reaction (PCR) in the AKR mouse and various cell lines, each of the H-2k haplotype. Our results show that Q5k mRNA is present during the whole postimplantational development of the AKR embryo/fetus (gestation day 6 to 15). In the juvenile mouse (week 2 to 4) transcription of the Q5k gene persisted in all organs examined. In contrast, in the adult animal expression of the Q5k gene was limited to the thymus and uterus of the pregnant mouse. Upon malignant transformation, the amount of Q5k-specific mRNA increased dramatically in thymus and could also be observed in the spleen of thymoma bearing animals. Expression of the Q5k gene was also detectable in several transformed mouse cell lines. Mitogen stimulation or treatment with cytokines induced Q5k expression in primary spleen cell cultures. A possible explanation for the tissue-restricted expression in the adult AKR mouse is discussed.