CLONING, CHROMOSOMAL LOCALIZATION, AND PHYSICAL LINKAGE OF THE BETA-SUBUNIT AND GAMMA-SUBUNIT (SCNN1B AND SCNN1G) OF THE HUMAN EPITHELIAL AMILORIDE-SENSITIVE SODIUM-CHANNEL

Three subunits of the amiloride-sensitive Na+ channel, named alpha, be ta, and gamma, have previously been cloned in rat colon. The human lun g alpha chain (SCNN1A) has also been cloned and its gene localized on chromosome 12p13. We now report the molecular cloning of the human lun g beta (SCNN1B) and gamma (SCNN1G) chains. In situ hybridization and p ulsed-field electrophoresis experiments demonstrate that both genes ar e located within a common 400-kb fragment on chromosome 16p12-p13. Scr eening of the cDNA library reveals two forms of the beta subunit that differ by the presence or absence of a 464-bp fragment in the 3' regio n. A frameshift in the short form modifies the COOH terminal sequence of the corresponding protein. Since several similar frameshifts mutati ons have recently been reported in patients affected by a rare form of hypertension, the existence of COOH truncated forms of the beta chain might be of physiological importance. (C) 1995 Academic Press, Inc.