Novel targeting strategy for generating mouse models with defects in the retinoid cycle

Carola Driessen1, Huub Winkens, Françoise Haeseleer

  • 1Department of Biochemistry (160), University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. c.driessen@ncmls.kun.nl

Vision Research
|November 13, 2003
PubMed

Insights

Researchers are developing gene-disrupted mice to study enzymes that oxidize 11-cis-retinol, crucial for vision. This research aims to identify key enzymes involved in visual cycle regulation and potential disease mechanisms.

Area of Science:

  • Biochemistry
  • Ophthalmology
  • Genetics

Background:

  • The visual cycle relies on the oxidation of 11-cis-retinol, a process primarily attributed to RDH5 but potentially involving other enzymes.
  • Retinal pigment epithelium, Müller cells, and photoreceptors contain enzymes capable of 11-cis-retinol oxidation, with candidate proteins now identified.

Purpose of the Study:

  • To investigate the physiological and pathological roles of enzymes involved in 11-cis-retinol oxidation beyond RDH5.
  • To determine if identified retinol dehydrogenases account for residual 11-cis-retinol oxidation in RDH5 knockout models.

Main Methods:

  • Development of a rapid gene-targeting strategy for creating gene-disrupted mice.
  • Generation of double and triple knockout mouse models to assess the function of multiple retinol dehydrogenases simultaneously.

Main Results:

  • Candidate proteins responsible for 11-cis-retinol oxidation have been identified.
  • Gene-disrupted mouse models, including double and triple knockouts, are being generated to facilitate functional studies.

Conclusions:

  • The generation of gene-disrupted mice is crucial for elucidating the specific roles of various retinol dehydrogenases in the visual cycle.
  • Understanding these enzymes' functions is vital for comprehending visual processing and developing therapeutic strategies for retinal diseases.