Genomic structure and precise mapping of a thymic regulatory region on mouse chromosome 17 revealed by a c-myc transgene insertion.
In one transgenic strain harboring a human c-myc proto-oncogene construct, the transgene was actively and exclusively expressed in the thymus, where it contributed to the development of lymphoma that corresponded to CD4(+)CD8(+) cells. Here, we have pursued the analysis of transgene expression in healthy transgenic mice and show that transgene activation occurs in the thymus 3 days before birth, at a time when CD4(+)CD8(+) lymphocytes emerge. In the adult, its expression is restricted to the CD4(+)CD8(+) cells. The region flanking the transgene insertion site was isolated and made it possible to map the preintegration locus, hereafter called Tsil (for thymus-specific integration locus) on chromosome 17 between D17Rp11e and Ras12-3. A YAC that contains both Tsil and the Pim2 locus, previously shown to be involved in progression of T-cell lymphoma, was isolated. Analysis of Tsil offers a unique opportunity to identify a regulatory region or a gene that might play an important role in T-cell maturation.
Lavenu
A
A
Department of Immunology, Institut Pasteur, 25 rue du Dr. Roux, Paris Cedex, 75724, France.
Roland
J
J
Poirier
C
C
Cazenave
P
P
Babinet
C
C
Morello
D
D
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens; D016827:CD8 Antigens; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D003433:Crosses, Genetic; D017931:DNA Primers; D005434:Flow Cytometry; D015870:Gene Expression; D016259:Genes, myc; D006720:Homozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011995:Recombination, Genetic; D015183:Restriction Mapping; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D017931:DNA Primers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc