Advertisement

Studies on the Metabolism of Retinol and Retinol-Binding Protein (RBP) in Transthyretin-Lacking Mice Produced by Homologous Recombination

  • S. Wei
  • V. Episkopou
  • R. Piantedosi
  • M. E. Gottesman
  • E. J. Robertson
  • W. S. Blaner
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 375)

Abstract

In the circulation, retinol-binding protein (RBP) is present as a one-to-one protein complex with transthyretin (TTR). It has been hypothesized that the binding of RBP to TTR prevents filtration of RBP in the kidney and may play a role in mediating the secretion of RBP from hepatocytes. To examine these possibilities, we have studied RBP metabolism and retinol metabolism in a strain of mice (aTTR) produced by targeted integration to lack TTR. In the plasma of aTTR and control mice, mean RBP levels (N = 6) were measured to be respectively, 0.11 ± 0.09 and 3.41 ± 1.21 mg RBP/dliter. Mean hepatic levels of RBP for the aTTR and control mice were respectively, 39.8 ± 4.5 and 25.0 ± 2.3 μg RBP/g tissue. Plasma retinol could not be detected (< 2.0 μg/dliter) in the aTTR mice; whereas, plasma retinol levels in control animals averaged 30.0 ± 1.2 μg/dliter. The level of retinol present in the livers of control mice was found to be 229.8 ± 29.6 μg retinol eq./g tissue. For the livers of aTTR mice, this level was found to be significantly elevated, at 505.5 ± 144.2 μg/g tissue. Urine levels of RBP appeared to be elevated in the aTTR mice. RBP mRNA levels in both the liver and adipose tissue of the aTTR and control mice were identical. In addition, tissue CRBP mRNA levels in the liver and testis, which are known to be regulated by retinoid availability, were the same for the aTTR and control animals. Our studies suggest that TTR prevents the filtration of RBP in the kidney and the elevated levels of retinol and RBP in the livers of the aTTR mice may suggest that TTR plays a role in aiding the secretion of RBP from the liver. However, since these animals have a normal phenotype, it would seem that even in the absence of TTR and with essentially no retinol or RBP, tissues are able to obtain sufficient retinoid to maintain normal function.

Keywords

mRNA Level Adipose Tissue Elevated Level Protein Complex Control Animal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • S. Wei
    • 1
  • V. Episkopou
    • 1
  • R. Piantedosi
    • 1
  • M. E. Gottesman
    • 1
  • E. J. Robertson
    • 1
  • W. S. Blaner
    • 1
  1. 1.College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

Personalised recommendations