Deletions within the mouse beta-globin locus control region preferentiallyreduce beta(min) globin gene expression

The mouse beta-globin gene cluster is regulated, at least in part, by a loc us control region (LCR) composed of several developmentally stable DNase I hypersensitive sites located upstream of the genes. In this report, we exam ine the level of expression of the beta(min) and beta(maj) genes in adult m ice in which HS2, HS3, or HS5,6 has been either deleted or replaced by a se lectable marker via homologous recombination in ES cells. Primer extension analysis of PNA extracted from circulating reticulocytes and HPLC analysis of globin chains from peripheral red blood cells revealed that all mutation s that reduce the overall output of the locus preferentially decrease beta( min) expression over beta(maj). The implications of these findings for the mechanism by which the LCR controls expression of the beta(maj) and beta(mi n) promoters are discussed. (C) 2000 Academic Press.