The Skn alloantigens of the mouse are strain-specific proteins confined to cells sharing a common ectodermal lineage (Rees et al. 1993;Jackman et al. 1989: Scheid et al. 1972). Proteins encoded by Skn are expressed in epidermal cells of skin and distinct populations of neural cells of adult mice, yet fail to accumulate in hematopoietic cells. As a consequence, Skn alloantigenic disparities between A/J (A) and C57BL/6 (B6) mice result in a tissue-restricted histoincompatibility between these strains such that lethally irradiated B6 mice reconstituted with spleen cells from (B6 ร A) F1 donors (denoted (B6 x A)/B6 chimeras), will inevitably reject skin grafts from A and (B6 x A) F1 mice, while accepting skin grafts from B6 mice (Boyse et al. 1970).
Skn alloantigens have been shown to be targets of skin-directed autoimmune responses (Jackman and Goldberg 1993) and are candidates as differentiation antigens directing the commitment of cells to specific cell lineages (Boyse et al. 1970;Rees et al. 1993). Earlier studies by Wachtel and co-workers (1977) in which skin from [(B6 x A) F1 x B6] backcross segregants was grafted to (B6 x A)/B6 chimeras showed that Skn antigens are encoded by two unlinked genes, Skn 1 and Skn 2, each with alternative alleles in A (Skn 1 a, Skn 2a; Skn 1.1 and Skn 2.1 alloantigens) and B6 mice (Skn i b, Skn 2b; Skn 2.1 and Skn 2.1 alloantigens); a disparity at either locus is sufficient to mediate a rejection response. Others, however, have argued that Skn is a genetically complex locus represented by multiple genes (Fleming and Silvers 1981).
In order to begin to resolve these issues as well as to provide a basis for characterizing strain-specific polymorphisms in Skn genes, we have initiated a molecular genetic characterization of the Skn histoincompatibility