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Gene Review

Slc9a4  -  solute carrier family 9 (sodium/hydrogen...

Mus musculus

Synonyms: AW990558, D730009J23Rik, NHE-4, NHE4, Na(+)/H(+) exchanger 4, ...
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High impact information on Slc9a4

  • Histological abnormalities were observed in the gastric mucosa of 9-week-old NHE4-/- mice, including sharply reduced numbers of parietal cells, a loss of mature chief cells, increased numbers of mucous and undifferentiated cells, and an increase in the number of necrotic and apoptotic cells [1].
  • Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger [1].
  • Analysis of stomach contents revealed that NHE4-/- mice were hypochlorhydric [1].
  • The NHE4 Na+/H+ exchanger is abundantly expressed on the basolateral membrane of gastric parietal cells [1].
  • Immunostaining showed that NHE1, NHE2, and NHE4 were present in both apical and basolateral membranes [2].

Biological context of Slc9a4


Anatomical context of Slc9a4

  • However, unlike NHE4 in other tissues, the MIA-resistant component did not transport Li+ in exchange for H+, and reverse transcription-polymerase chain reaction detected NHE4 mRNA in the oocyte but not in later stages [5].
  • MKTAL cells express NHE2 and NHE1 proteins but not NHE3 and NHE4, whereby NHE2 protein is expressed selectively in the apical domain of the plasma membrane [6].
  • In two types of epithelial cells, kidney and stomach, NHE4 is localized to the basolateral membrane [4].
  • By Western blot analysis, NHE4 was identified as a 65- to 70-kDa protein that was expressed most abundantly in stomach and in multiple additional epithelial and nonepithelial rat tissues including skeletal muscle, heart, kidney, uterus, and liver [4].

Associations of Slc9a4 with chemical compounds

  • The results indicate that the basolaterally located NHE1, NHE2, and NHE4, in addition to participating in the homeostatic control of intracellular pH, may play a role in H(+) extrusion in order to achieve transepithelial HCO(3)(-) secretion [2].
  • The MIA-resistant component was inhibited by 2 mM amiloride and enhanced by external K+ and by 4,4'-diisothiocyanostilbene-2,2'-disulfonate, suggesting NHE4 activity [5].

Other interactions of Slc9a4

  • The relative contribution of the different isoforms to pH(i)- and hyperosmolarity-activated Na(+)/H(+) exchange in the different cell types paralleled their relative expression levels. cAMP elevation also stimulated NHE4, whereas an increase in osmolarity above a certain threshold further increased NHE1 and not NHE4 activity [3].

Analytical, diagnostic and therapeutic context of Slc9a4


  1. Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. Gawenis, L.R., Greeb, J.M., Prasad, V., Grisham, C., Sanford, L.P., Doetschman, T., Andringa, A., Miller, M.L., Shull, G.E. J. Biol. Chem. (2005) [Pubmed]
  2. Expression, immunolocalization, and functional activity of Na+/H+ exchanger isoforms in mouse endometrial epithelium. Wang, X.F., Yu, M.K., Lam, S.Y., Leung, K.M., Jiang, J.L., Leung, P.S., Ko, W.H., Leung, P.Y., Chew, S.B., Liu, C.Q., Tse, C.M., Chan, H.C. Biol. Reprod. (2003) [Pubmed]
  3. Differential expression and regulation of Na(+)/H(+) exchanger isoforms in rabbit parietal and mucous cells. Rossmann, H., Sonnentag, T., Heinzmann, A., Seidler, B., Bachmann, O., Vieillard-Baron, D., Gregor, M., Seidler, U. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  4. Immunochemical characterization of Na+/H+ exchanger isoform NHE4. Pizzonia, J.H., Biemesderfer, D., Abu-Alfa, A.K., Wu, M.S., Exner, M., Isenring, P., Igarashi, P., Aronson, P.S. Am. J. Physiol. (1998) [Pubmed]
  5. Developmental changes in the management of acid loads during preimplantation mouse development. Harding, E.A., Gibb, C.A., Johnson, M.H., Cook, D.I., Day, M.L. Biol. Reprod. (2002) [Pubmed]
  6. Differentiated thick ascending limb (TAL) cultured cells derived from SV40 transgenic mice express functional apical NHE2 isoform: effect of nitric oxide. Bourgeois, S., Rossignol, P., Grelac, F., Chalumeau, C., Klein, C., Laghmani, K., Chambrey, R., Bruneval, P., Duong, J.P., Poggioli, J., Houillier, P., Paillard, M., Kellermann, O., Froissart, M. Pflugers Arch. (2003) [Pubmed]
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