Lymphoid specificity of a copy number-related expression of the H2-Kb transgene

Transcriptional regulation of the MHC class I genes leading to their developmental and tissue specific expression is still poorly understood in spite of the recovery of a large variety of cis-controlling sequences and trans-acting factors pertaining to the 5' enhancer and the downstream regulatory element. Here we produced a series transgenic lines of mice with a genomic subclone of the H2-Kb gene consisting of 367 bp of the 5' upstream region, the coding region and 1.5 kb of the 3' downstream region and carrying all hitherto known regulatory sequences. The comparison of nine transgenic lines carrying the same H2-Kb transgene made it possible to ask whether the cis-information present in the transgene was sufficient for the tissue- and developmental-specific expression and its copy number dependence. We found the proper developmental onset of expression of the transgene at day 13 p.c. and correct tissue specific mRNA levels in adult mice. While in lymphoid tissues and in lung the number of transgene copies still correlated with RNA levels, the copy number dependence was completely lost in liver, kidney and embryonic tissues. Comparison with previously published H2-Kb transgenes indicates that the H2-Kb locus-controlling region is composed of more than one element.