Conditional loss of Kcnj13 in the retinal pigment epithelium causes photoreceptor degeneration

Exp Eye Res. 2018 Nov;176:219-226. doi: 10.1016/j.exer.2018.07.014. Epub 2018 Jul 25.


The retina is the light sensing tissue of the eye which contains multiple layers of cells required for the detection and transmission of a visual signal. Loss of the light-sensing photoreceptors leads to defects in visual function and blindness. Previously, we found that mosaic deletion of Kcnj13, and subsequent loss of the potassium channel Kir7.1, in mice leads to photoreceptor degeneration and recapitulates the human retinal disease phenotype (Zhong et al., 2015). Kcnj13 expression in the retinal pigment epithelium (RPE) is essential for normal retinal electrophysiology, function, and survival. Mice with homozygous loss of Kcnj13 die at postnatal day 1 (P1), requiring a tissue-specific approach to study retinal degeneration phenotypes in adult mice. We used the CRISPR-Cas9 system to generate a floxed, conditional loss-of-function (cKO) Kcnj13flox allele to study the pathogenesis of Kcnj13 deficiency in the retina. To investigate if the Kcnj13 is required in the RPE for photoreceptor function and survival, we used Best1-cre, which is specifically expressed in the RPE. We observed complete loss of Kcnj13 expression in Cre-positive RPE cells. Furthermore, our findings show that widespread loss of Kcnj13 in the RPE leads to severe and progressive thinning of the outer nuclear layer and a reduced response to light. Finally, to detect Best1-cre expression in the RPE of live animals without sacrificing the animal for histology, we generated a Cre-reporter-containing Kcnj13 cKO mouse line (cKOR: Kcnj13flox/flox; Best1-cre; Ai9) which can be rapidly screened using retinal fluorescence microscopy. These findings provide new tools for studying the roles of Kcnj13 in retinal homeostasis.

Keywords: Conditional knockout; KCNJ13; Kir7.1; Leber congenital amaurosis; Photoreceptors; RPE; Retinal degeneration; Retinal function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Associated Protein 9
  • Electroretinography
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Photoreceptor Cells, Vertebrate / pathology*
  • Potassium Channels, Inwardly Rectifying / physiology*
  • Retina / physiopathology
  • Retinal Degeneration / pathology*
  • Retinal Pigment Epithelium / metabolism*


  • Kir7.1 channel
  • Potassium Channels, Inwardly Rectifying
  • CRISPR-Associated Protein 9