April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Abnormal synaptic transmission between photoreceptors and bipolar cells in DHDDSK42E/K42E mice
Author Affiliations & Notes
  • Rong Wen
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Byron L Lam
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Ziqiang Guan
    Biochemistry, Duke University Medical Center, Durham, NC
  • Zhengying Wang
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Ning Wang
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Yihui Chen
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Yiwen Li
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 716. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Rong Wen, Byron L Lam, Ziqiang Guan, Zhengying Wang, Ning Wang, Yihui Chen, Yiwen Li; Abnormal synaptic transmission between photoreceptors and bipolar cells in DHDDSK42E/K42E mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):716.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: We recently identified a single-nucleotide mutation c.124A>G in the DHDDS gene encoding dehydrodolichol diphosphate synthase (DHDDS), which changes a highly conserved Lys42 to Glu and is responsible for 12% of autosomal recessive RP (arRP) cases in patients of Ashkenazi Jewish (AJ) origin. The present work characterizes electrophysiological changes in recently created DHDDSK42E/K42E mice.

Methods: Transgenic mice with DHDDSK42E genotype were created by the knock-in (KI) technology and bred into homozygosity. Lipids were extracted from plasma and dolichols were measured by liquid chromatography-mass spectrometry (LC-MS). Scotopic full-field ERGs were recorded from 3 month old DHDDSK42E/K42E mice and compared to age-matched wild-type (wt) animals.

Results: The DHDDSK42E/K42E genotype was confirmed by PCR. A characteristic shortening of dolichol length distribution was found in the plasma of DHDDSK42E/K42E mice, similar to what was found in patients. Dolichol 17 (D17) became the dominant species in the mutant mice instead of dolichol 18 (D18) in wt animals. As a result, the DHDDSK42E/K42E mice have much higher plasma D17/D18 ratio. The ERG a-wave in the DHDDSK42E/K42E mice was smaller than a-wave of the wt controls, and the b-wave was disproportionally smaller with the b- to a-wave amplitude ratio being close to 1. In contrast, the ratio was more than 2 in the wt controls.

Conclusions: These results indicate that abnormal dolichol biosynthesis by the K42E DHDDS mutation leads to impaired synaptic transmission between photoreceptors and bipolar cells. Previous studies using artificial membrane suggest a potential role of dolichols in facilitating vesicle fusion. Our results provide the first in vivo evidence supporting a biological function of free dolichols in the activities of synaptic vesicles.

Keywords: 695 retinal degenerations: cell biology • 510 electroretinography: non-clinical • 696 retinal degenerations: hereditary  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×