Genetic ablation of Rhbg in the mouse does not impair renal ammonium excretion.
NH(4)(+) transport by the distal nephron and NH(4)(+) detoxification by the liver are critical for achieving regulation of acid-base balance and to avoid hyperammonemic hepatic encephalopathy, respectively. Therefore, it has been proposed that rhesus type B glycoprotein (Rhbg), a member of the Mep/Amt/Rh NH(3) channel superfamily, may be involved in some forms of distal tubular acidosis and congenital hyperammonemia. We have tested this hypothesis by inactivating the RHbg gene in the mouse by insertional mutagenesis. Histochemical studies analyses confirmed that RHbg knockout (KO) mice did not express Rhbg protein. Under basal conditions, the KO mice did not exhibit encephalopathy and survived well. They did not exhibit hallmarks of distal tubular acidosis because neither acid-base status, serum potassium concentration, nor bone mineral density was altered by RHbg disruption. They did not have hyperammonemia or disturbed hepatic NH(3) metabolism. Moreover, the KO mice adapted to a chronic acid-loading challenge by increasing urinary NH(4)(+) excretion as well as their wild-type controls. Finally, transepithelial NH(3) diffusive permeability, or NH(3) and NH(4)(+) entry across the basolateral membrane of cortical collecting duct cells, measured by in vitro microperfusion of collecting duct from KO and wild-type mice, was identical with no apparent effect of the absence of Rhbg protein. We conclude that Rhbg is not a critical determinant of NH(4)(+) excretion by the kidney and of NH(4)(+) detoxification by the liver in vivo.
Chambrey
Régine
R
INSERM U652, IFR58, Institut des Cordeliers, Paris, France. chambrey@ccr.jussieu.fr
Goossens
Dominique
D
Bourgeois
Soline
S
Picard
Nicolas
N
Bloch-Faure
May
M
Leviel
Françoise
F
Geoffroy
Valérie
V
Cambillau
Michele
M
Colin
Yves
Y
Paillard
Michel
M
Houillier
Pascal
P
Cartron
Jean Pierre
JP
Eladari
Dominique
D
D000141:Acidosis, Renal Tubular / Q000503:physiopathology; D000641:Ammonia / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D015519:Bone Density; D006023:Glycoproteins / Q000235:genetics*; D007668:Kidney / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D006180:Proton-Translocating ATPases / Q000096:biosynthesis
D001457:Anion Exchange Protein 1, Erythrocyte; D006023:Glycoproteins; D026901:Membrane Transport Proteins; C486033:RhBG protein, mouse; D000641:Ammonia; D006180:Proton-Translocating ATPases