Retinol-binding protein-deficient mice: biochemical basis for impaired vision

Biochemistry. 2002 Dec 24;41(51):15360-8. doi: 10.1021/bi0268551.

Abstract

We reported previously that mice lacking plasma retinol-binding protein (RBP) are phenotypically normal except that they display impaired vision at the time of weaning. This visual defect is associated with greatly diminished eyecup levels of retinaldehyde and is reversible if the mutants are maintained for several months on a vitamin A-sufficient diet. Here we provide a biochemical basis for the visual phenotype of RBP-deficient mice. This phenotype does not result from inadequate milk total retinol levels since these are not different for RBP-deficient and wild-type mice. The eye, unlike all other tissues that have been examined, takes up dietary retinol very poorly. Moreover, compared to other tissues, the eye displays a strong preference for retinol uptake when retinol is delivered bound to RBP. The poor uptake of dietary retinol by the eye coupled with its marked ability to take up retinol from RBP, we propose, provides a basis for the impaired vision observed in weanling RBP-deficient mice. Further study of the mutants suggests that the impaired vision is reversible because the eyes of mutant mice slowly acquire sufficient retinol from the low levels of retinol present in their circulation either bound to albumin or present in lipoprotein fractions. Thus, the eye is unlike other tissues in the body in that it shows a very marked preference for acquiring retinol needed to support vision from the retinol-RBP complex and is unable to meet adequately its retinol need through uptake of recently absorbed dietary retinol. This provides an explanation for the impaired vision phenotype of RBP-deficient mice.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Animals, Suckling
  • Female
  • Injections, Intravenous
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Milk / chemistry
  • Phenotype
  • Retinoids / blood
  • Retinoids / pharmacokinetics
  • Retinol-Binding Proteins / chemistry
  • Retinol-Binding Proteins / deficiency*
  • Retinol-Binding Proteins / genetics*
  • Retinol-Binding Proteins, Plasma
  • Vision Disorders / genetics*
  • Vision Disorders / metabolism
  • Vitamin A / pharmacokinetics

Substances

  • Retinoids
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Plasma
  • Vitamin A