PubMed · 7990898
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D Tolchin. 1995-01-12. Clinical problem-solving: invasive interventions.. https://pubmed.ncbi.nlm.nih.gov/7990898/
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We have examined the role of the AP-1 transcription factor on thymocyte maturation and thymus architecture by overexpressing FosB2 in transgenic mice. FosB2 is a naturally occurring splice variant of the FosB2 gene, encoding a truncated protein which lacks two domains necessary for transcriptional activation. The expression of FosB2 in the thymocytes severely affected their maturation and the structure of the whole thymus: the phenotype developed slowly during the first months of life, resulting in a progressive expansion of the medulla and concomitant reduction of the cortex. CD4+ thymocytes represented the major thymocyte population, whereas the CD4+ 8+ thymocytes were virtually absent. This phenotype appeared to be an intrinsic property of bone marrow derived cells, as it could be reproduced in bone marrow chimaeric mice. This pathology was very reminiscent to that observed in mice overexpressing c-Fos in thymic epithelium: also in that case the thymus underwent with age a progressive expansion of the epithelium and major changes in the ratio of thymocyte subsets, but the phenotype appeared to be an intrinsic property of the epithelial cells since it could not be reproduced by transgenic bone marrow transplantation. We speculate that both overexpression of FosB2 in thymocytes and overexpression of c-Fos in thymic epithelium results in aberrant signaling between thymocytes and stroma, that ultimately alters the thymic micromilieu, leading to this severe pathology.
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By employing dual-digitonin-pulse perfusion technique, the cytosolic fractions were prepared from periportal (PP) and perivenous (PV) hepatocytes of male and female rat livers. Sulfotransferase (ST) activities toward 2-naphthol (2NAP) (at pH 5.5 and 7.4), 4-nitrophenol, dehydroepiandrosterone (DHEA), and cortisol were measured in each fraction. DHEA-ST activity was mainly localized in PP fraction in males, while in females it was slightly higher in PP fraction than in PV samples. In contrast, phenol ST activities were higher in PV fraction in both sexes. With anti-HS-ST and anti-P-ST antisera, the levels of immunoreactive ST polypeptides were compatible with the levels of ST activities except that in female PP fraction the level of immunoreactive P-ST polypeptide was low in spite of comparatively high levels of P-ST activities. Chromatofocusing of PP and PV fractions separated P-ST activities into three major fractions (I-III), which have distinct catalytic and electrochemical properties. Fraction I was localized only in the PP samples in both sexes and revealed ST activities toward 2NAP at pH 5.5 and 7.4, while fraction II was localized in the PP and PV samples in both sexes with 2NAP-ST activity only at pH 7.4. Fraction III which had ST activities at pH 5.5 and 7.4 was present only in the PV samples in female rats, whereas in male rats it was present in both PP and PV samples. With anti-P-ST antiserum, the immunoreactive polypeptide was present in fraction III, but no immunoreactive band was detected in fractions I and II, suggesting the presence of immunochemically and electrochemically different P-ST(s) in these fractions.