A highly divergent member of the MHC class I gene family, Ml, is representative of a small sub-family of three sequences. Ml itself appears to be a direct descendant of a primordial class I gene, which antedates speciation. Ml has been mapped to a region of chromosom 17 telomeric to Qa and has been used to define a new subregion, M. The other two members of the sub-family, M2 and M3, are also highly divergent from the rest of the class I family, but are also divergent from Ml and one another. Like Ml, both M2 and M3 contain open reading frames and legitimate splice sites in all exons. Ml appears to contain a functional promoter, since introduction into fibroblasts of a 3.4 kb fragment of DNA containing the MI coding sequences results in Ml expression. Similarly, the Ml promoter, ligated to the CAT reporter gene, is able to direct CAT enzyme expression. However, Ml is not detectably transcribed in vivo in a variety of cell lines or adult tissues, as assessed by PCR analysis. Expression of Ml is controlled by a strong silencer element located within a 16 kb genomic fragment containing the Ml gene. The patterns of expression of M2 and M3 are under investigation. No Ml antigen has been identified to date. To attempt to generate Ml product, transgenic mice have been produced in which Ml expression is directed by a viral LTR promoter. Similar transgenic lines have been produced using the truncated Ml promoter. Analysis of the expression of Ml in these lines is in progress.
