This is a proposal to investigate the genetic regulation and linkage of the red blood cell intermediate 2,3-diphosphoglycerate among inbred strains of mice. DPG is known to have a profound effect on the affinity of the red blood cell for oxygen and is implicated in other significant aspects of metabolism including the level of serum chlosterol. The level of DPG in the red blood cell are influenced by both the environment and genetics. Using outbred lines of rats, selection of lines with high and low levels of DPG has been achieved. Also, a major DPG locus has been identified near the beta hemoglobin locus. Inbred mice provide a mechanism to establish more precisely the genetic effects of a single locus, and through crosses and the use of recombinant inbred lines to determine linkage. The conservation of linkage groups suggest a functional or regulatory relationship among the loci conserved. If linkage is conserved between DPG and beta hemoglobin, this would be of particular significance, since DPG binds to the beta hemoglogin within the cell. In addition genetic variation and linkage of DPG will be investigated in the cricetid rodent Peromyscus. This will provide more information on the genetic variability of DPG and the possible conservation of linkage between DPG and B-hemoglobin, for which a gene has been identified in Peromyscus. These studies should provide information on the genetics and regulation of DPG which could form the basis of extensive investigations of the effects of this intermediate within the erythrocyte. In addition they have the potential to expand the gene map and enhance the knowledge of linkage in association with function.