Different regulation of class I gene expression in the adult mouse and during development

The expression of the class I genes encoding for histocompatibility Ag is complex both in adult and during development. Although ubiquitously expressed in the adult, the mRNA level of class I genes is variable from one organ to another. During development, H-2K mRNA expression has two phases: the first from blastocyst to day 11, where H-2K mRNA level is extremely low, and the second, beginning after day 11, when H-2K mRNA expression increases first dramatically (10x) and then progressively to birth. To localize the sequences responsible for the regulation of H-2K gene expression in the adult and during development, we have constructed a series of transgenic strains carrying 1) a 9-kb native H-2K gene, H-2K LF, corresponding to the entire H-2Kb gene with 2 kb of upstream sequences and 3 kb of downstream sequences, and 2) two hybrid constructs linking the same 5'-flanking region of H-2Kb gene to two reporter genes, the human growth hormone and the human c-myc proto-oncogene. Expression of the transgenes was compared with that of the endogeneous H-2K gene in adult organs and during development of the different transgenic strains. In the adult, the three constructs behave almost like the endogeneous H-2K gene, but the H-2K LF construct is the only one whose expression is independent of the integration site and related to the copy number. During development, both fusion genes are barely expressed in the embryo as well as in the extra-embryonic tissues, whereas the H-2K LF transgene expression parallels that of the endogeneous class I gene. Therefore, our results show that H-2K developmental regulatory sequences are not included in the region that controls H-2K mRNA expression in the adult, indicating that H-2K class I gene expression in adult organs and in development is regulated by different mechanisms.