Studies on the metabolism of retinol and retinol-binding protein in transthyretin-deficient mice produced by homologous recombination.
Tissue needs for retinoids are believed to be satisfied through the delivery in the circulation of retinol by its specific plasma transport protein, retinol-binding protein (RBP), which circulates as a 1-to-1 protein complex with transthyretin (TTR). The binding of RBP to TTR is thought to prevent filtration of retinol-RBP in the kidney and to play a role in secretion of RBP from hepatocytes. Recently a strain of mice (TTR-) that totally lacks immunoreactive TTR was produced by targeted mutagenesis. We have explored the effects of TTR deficiency on retinol and RBP metabolism in this mutant strain. In pooled plasma from the TTR- mice retinol levels averaged 6% of those of wild type animals. Similarly, plasma RBP in the TTR- mice was found to be 5% of wild type levels. Hepatic retinol and retinyl ester levels were similar for mutant and wild type mice, suggesting that the mutation affects neither the uptake nor storage of dietary retinol. Levels of retinol and retinyl esters in testis, kidney, spleen, and eye cups from TTR- mice were normal. Plasma all-trans-retinoic acid levels for the TTR- mice were 2.3-fold higher than those of wild type (425 versus 190 ng/dl). Kidney RBP levels were similar for the mutant and wild type mice and we were unable to detect intact RBP in urine from TTR- mice. Hepatic RBP levels in the TTR- mice were 60% higher than those of wild type mice (39.8 versus 25.0 micrograms of RBP/g of tissue). These data may suggest that there is a partial blockage in RBP secretion from TTR- hepatocytes that leads to lessened plasma levels of retinol-RBP.
Wei
S
S
Institute of Human Nutrition, Columbia University, New York, New York 10032.
Episkopou
V
V
Piantedosi
R
R
Maeda
S
S
Shimada
K
K
Gottesman
M E
ME
Blaner
W S
WS
D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D017931:DNA Primers; D005123:Eye / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011228:Prealbumin / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D054839:Retinol-Binding Proteins, Plasma; D013154:Spleen / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism*
D017931:DNA Primers; D011228:Prealbumin; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A