Structure of wild-type and mutant mouse beta 2-microglobulin genes.

beta 2-Microglobulin is encoded by a single gene per haploid genome in the mouse. This gene was cloned and sequenced and was shown to consist of four coding regions separated by three intervening sequences. Most of the protein (amino acids 3-95) is encoded in a single uninterrupted unit flanked by intervening sequences. In this respect, the genetic organization is similar to that of the evolutionarily related H-2 and immunoglobulin domains. A mutant cell line selected for loss of cell-surface expression of the thymus leukemic antigen and failing to express surface beta 2-microglobulin and H-2 was found to contain no detectable cytoplasmic beta 2-microglobulin. The genetic defect in this mutant was analyzed by Southern blots, which indicated that there are defects in both copies of the beta 2-microglobulin gene present in this cell. The concomitant loss of three cell-surface antigens was thereby linked to genetic defects in the beta 2-microglobulin locus.