Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice

Hoon Shim, Chih Ting Wang, Yen Lin Chen, Viet Q. Chau, Kevin G. Fu, Jianqi Yang, A. Rory McQuiston, Rory A. Fisher, Ching Kang Chen

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Two members of the R7 subfamily of regulators of G protein signaling, RGS7 and RGS11, are present at dendritic tips of retinal depolarizing bipolar cells (DBCs). Their involvement in the mGluR6/Gαo/TRPM1 pathway that mediates DBC light responses has been implicated. However, previous genetic studies employed an RGS7 mutant mouse that is hypomorphic, and hence the exact role of RGS7 in DBCs remains unclear.Wehave made a true RGS7-null mouse line with exons 6-8 deleted. The RGS7-/- mouse is viable and fertile but smaller in body size. Electroretinogram (ERG) b-wave implicit time in young RGS7-/- mice is prolonged at eye opening, but the phenotype disappears at 2 months of age. Expression levels of RGS6 and RGS11 are unchanged in RGS7-/- retina, but the Gβ5S level is significantly reduced. By characterizing a complete RGS7 and RGS11 double knock-out (711dKO) mouse line, we found that Gβ5S expression in the retinal outer plexiform layer is eliminated, as is theERGb-wave. Ultrastructural defects akin to those of Gβ5-/- mice are evident in 711dKO mice. In retinas of mice lacking RGS6, RGS7, and RGS11,Gβ5S is undetectable, whereas levels of the photoreceptor-specific Gβ5L remain unchanged. Whereas RGS6 alone sustains a significant amount of Gβ5S expression in retina, the DBC-related defects in Gβ5-/- mice are caused solely by a combined loss of RGS7 and RGS11. Our data support the notion that the role of Gβ5 in the retina, and likely in the entire nervous system, is mediated exclusively by R7 RGS proteins.

Original languageEnglish (US)
Pages (from-to)14873-14879
Number of pages7
JournalJournal of Biological Chemistry
Volume287
Issue number18
DOIs
StatePublished - Apr 27 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice'. Together they form a unique fingerprint.

Cite this