A F2 population derived from a cross between European Large White and Chinese Meishan pigs was established in order to study the genetic basis of breed differences for growth and fat traits. Chromosome 4 was chosen for initial study as previous work had revealed quantitative trait loci (QTLs) on this chromosome affected growth and fat traits in a Wild Boar x Large White cross. Individuals in the F2 population were typed for nine markers spanning a region of approximately 124 CM. We found evidence for QTLs affecting growth between weaning and the end of test (additive effect: 43.4 g/day) and fat depth measured in the mid-back position (additive effect: 1.82 mm). There was no evidence of interactions between the QTLs and sex, grandparents or F1 sires, suggesting that the detected QTLs were fixed for alternative alleles in the Meishan and Large White breeds. Comparison of locations suggests that these QTLs could be the same as those found in the Wild Boar x Large White cross.

The effects of recombinant human interleukin 3 (IL3) on normal bone marrow cells and human leukemic cells were studied. In clonal assays, IL3 supported the growth of all colony types including megakaryocytes. Erythroid colonies were formed in the presence of IL3 and erythropoietin, but not in the absence of erythropoietin. Replating experiments using blast cell colonies derived from a cell population enriched for progenitor cells by fluorescence-activated cell sorting with the monoclonal antibody 3C5, showed that IL3 supported the continued replating of colonies. The clonal proliferation of human bone marrow cells in response to IL3 was inhibited by tumor necrosis factor and by lymphotoxin, but not by interferon-gamma. In suspension cultures, IL3 supported the proliferation of mast cells. Human IL3 had no effect on the growth responses, morphology, cytochemistry, or clonogenicity of the human leukemic cell lines HL60, U-937, KG1a, and HEL. Transcripts for IL3 mRNA were not detectable in these cells, nor in the K562 cell line, implying that autocrine secretion of IL3 was not the mechanism by which these leukemias were maintained. Although cells derived from the bone marrow or peripheral blood of twenty patients with myeloproliferative disorders, myelodysplastic syndromes or acute myeloid leukemia frequently showed proliferative responses to IL3, mRNA transcripts for IL3 were not detected in these cells.

The mechanisms that regulate thymocyte proliferation and differentiation within the thymus are still poorly understood. As a novel approach to analyzing these problems, we have used a retroviral vector to insert oncogenes into fetal thymic cells, and construct a library of thymic cell lines. Infection with a double promoter recombinant retrovirus containing the v-Ha-ras and v-myc oncogenes resulted in the apparent immortalization of a range of cell lines derived from 13- and 14-day murine fetal thymus, and expressing both v-Ha-ras and v-myc mRNA at high levels. Cell lines were established from untreated thymic lobes (group 1), deoxyguanosine-treated lobes (group 2), and in the presence of IL-2 (group 3). Cell lines with a wide range of surface phenotypes were established. Group 1 were adherent cell lines expressing many antigens, including Mac-1, FcR, and Ia. Group 2 were also adherent cells but expressed very few Ag. Group 3 were IL-2-dependent lymphoid-like non-adherent cells, with a null or early thymocyte-like phenotype. None demonstrated full rearrangement and expression of TCR alpha-, beta-, or gamma-genes, although cell lines in group 2 expressed short beta and those in group 3, short beta and gamma gene transcripts. This library of immortalized cell lines appears to represent several types of stromal cell and early thymocyte precursors present in 13- and 14-day fetal thymus. These cell lines should prove invaluable in reconstructing the environment of the intact fetal thymic lobe, to study the cellular interactions that appear to govern thymocyte proliferation, development, and selection of Ag reactivity.

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