title: NHE8 is essential for RPE cell polarity and photoreceptor survival.
abstract: A new N-ethyl-N-nitrosourea (ENU)-induced mouse recessive mutation, identified by fundus examination of the eye, develops depigmented patches, indicating retinal disorder. Histology data show aberrant retinal pigment epithelium (RPE) and late-onset photoreceptor cell loss in the mutant retina. Chromosomal mapping and DNA sequencing reveal a point mutation (T to A) of the Slc9a8 gene, resulting in mutant sodium/proton exchanger 8 (NHE8)-M120K protein. The lysine substitution decreases the probability of forming the 3(rd) transmembrane helix, which impairs the pore structure of the Na(+)/H(+) exchanger. Various RPE defects, including mislocalization of the apical marker ezrin, and disrupted apical microvilli and basal infoldings are observed in mutant mice. We have further generated NHE8 knockout mice and confirmed similar phenotypes, including abnormal RPE cells and late-onset photoreceptor cell loss. Both in vivo and in vitro data indicate that NHE8 co-localizes with ER, Golgi and intracellular vesicles in RPE cells. Thus, NHE8 function is necessary for the survival of photoreceptor cells and NHE8 is important for RPE cell polarity and function. Dysfunctional RPE may ultimately lead to photoreceptor cell death in the NHE8 mutants. Further studies will be needed to elucidate whether or not NHE8 regulates pH homeostasis in the protein secretory pathways of RPE.
authors: School of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Chun-hong
authors: CH
authors: Xia
authors: School of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Haiquan
authors: H
authors: Liu
authors: School of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Debra
authors: D
authors: Cheung
authors: School of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Felicia
authors: F
authors: Tang
authors: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors: Bo
authors: B
authors: Chang
authors: School of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Mei
authors: M
authors: Li
authors: School of Optometry and Vision Science Program, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Xiaohua
authors: X
authors: Gong
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D051379:Mice; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology*; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000502:physiology*
chemical_list: C471945:Slc9a8 protein, mouse; D017923:Sodium-Hydrogen Exchangers