Transgenic mice mimic the methylation pattern of the human HLA-DR alpha gene.

The methylation pattern of the human HLA-DR alpha gene has been studied in different tissues of transgenic mice. Offspring from two transgenic lines was selected for this analysis, carrying the integrated HLA-DR alpha gene in either single or multiple (8-10) copies per diploid genome. In transgenic animals two distinct methylation patterns of the HLA-DR alpha gene are generated, due to a complete methylation of all the GCGC and CCGG sites the former, and to unmethylation restricted to one or both the GCGC sites located in the 5' portion of the HLA-DR alpha gene, the latter. Unmethylation restricted to the 5' portion of the HLA-DR alpha gene is a highly conserved feature in human tissues and in vitro cultured cell lines; therefore, it is concluded that the methylation pattern of the human HLA-DR alpha transgene may be faithfully reconstituted in transgenic animals. Northern blotting analysis of the RNA isolated from tissues of the transgenic mouse carrying single-copy HLA-DR alpha transgene demonstrates its tissue specific expression, suggesting that transgenic mice may represent an "in vivo" experimental system to study the relationship between methylation state and transcriptional activation.