Structure and genetic polymorphism of the mouse KCC1 gene

The KCCl K-Cl cotransporter is a major regulator of erythroid and non-eryth roid cell volume, and the KCCl gene is a candidate modifier gene for sickle cell disease and other hemoglobinopathies. We have cloned and sequenced th e mouse KCCl (mKCCl) gene, defined its intron-exon junctions, and analyzed (AC)/(TG) intragenic polymorphisms. A highly polymorphic (AC) repeat of mKC Cl intron 1 was characterized in musculus strains, and used to prove lack o f linkage between the mKCC1 gene and the vol (resistant to osmotic lysis) l ocus. The intron 1 (AC) repeat in CAST/Ei and SPRET/Ei was not only more di vergent in length but also underwent additional sequence variation. A dimor phic (TG) repeat in intron 2 distinguished CAST/Ei from other strains, and an intron 17 B1 Alu-like SINE present in all musculus strains was found to be absent from intron 17 in SPRET/Ei. These and additional described strain -specific polymorphisms will be useful mapping and genetic tools in the stu dy of mouse models of sickle cell disease. (C) 2000 Elsevier Science B.V. A ll rights reserved.