THE ALPHA-SUBUNIT OF THE EPITHELIAL SODIUM-CHANNEL IN THE MOUSE - DEVELOPMENTAL REGULATION OF ITS EXPRESSION

Sodium reabsorption by the amiloride-sensitive sodium channel of epith elial cells plays a crucial role in the management of ionic compositio n and fluid Volume in the body. In the respiratory system, sodium tran sport is involved in the clearance of pulmonary edema and of liquid se creted during fetal life at birth; We have cloned a partial cDNA of th e alpha subunit of the mouse amiloride-sensitive sodium channel (alpha mENaC). In the region of comparison, the mouse alpha subunit shows 92 % identity at the DNA level and 95% identity at the amino acid level w ith the rat sequence. The kidneys, lungs, and distal colon are major s ites of expression of a 3.5-kb alpha mENaC mRNA, During mouse developm ent, alpha mENaC transcripts appear late during gestation (d 17.5) and are expressed continuously thereafter. In the distal colon, a short 1 .2-kb mRNA deleted of the 5' part of the transcript is detected during gestation and is replaced gradually by the mature 3.5-kb transcript a fter birth. alpha mENaC and alpha(1) Na+-K+-ATPase mRNAs have an expre ssion profile that is modulated similarly during development for a giv en tissue. The expression of alpha mENaC transcripts increases transie ntly in the lungs at birth (2.5-foId), as for alpha(1) Na+-K+-ATPase m RNAs (1.5-fold), suggesting that the expression of several components of the sodium transport system is modulated in the lungs at that time. In the kidney, there is no significant increase of alpha mENaC and al pha(1) Na+-K+-ATPase mRNAs in newborns.