Lymphoproliferative syndrome associated with c-myc expression driven by a class I gene promoter in transgenic mice.
We have produced transgenic mice carrying an H-2K/human c-myc fusion gene. In this construct, the human c-myc proto-oncogene expression is driven by the 5' flanking sequences (including promoter) of the class I H-2Kb gene, which have previously been shown to direct the expression of a marker gene, the human growth hormone (hGH), in most tissues of H-2K/hGH transgenic mice. Comparative analysis, by S1 nuclease mapping, of the H-2K and human c-myc gene expression in different organs of the H-2K/myc mice shows that exogenous c-myc and endogenous H-2K expression is found in most organs examined. However, the liver is a notable exception, for here c-myc expression is very weak. The exogenous c-myc expression is maximal in lymphoid organs of all H-2K/myc transgenic strains. One strain, H-2K/myc 27, hereditarily develops a lymphoproliferative syndrome which eventually leads to death. The H-2K/myc 27 lymphoid tissues are profoundly abnormal: pre-B cells as well as mature B cells are underrepresented in the bone marrow but the thymus as well as lymph nodes are largely infiltrated by B cells. Moreover, in the thymus, the proportions of the different thymic cell populations are altered. However, in the other H-2K/myc transgenic strains, even in those expressing a comparable or even higher level of myc, no pathology has been observed over a period of 20 months. Our results, therefore, demonstrate that constitutive enforced c-myc expression might disturb lymphocyte development, but does not directly lead to malignancy.
Morello
D
D
Department of Immunology, Institut Pasteur, Paris, France.
Lavenu
A
A
Bandeira
A
A
Portnoi
D
D
Gaillard
J
J
Babinet
C
C
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D006183:H-2 Antigens / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia; D008198:Lymph Nodes / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D013950:Thymus Gland / Q000473:pathology
D006183:H-2 Antigens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc