G. Troen et al., Vitamin A-sensitive tissues in transgenic mice expressing high levels of human cellular retinol-binding protein type I are not altered phenotypically, J NUTR, 129(9), 1999, pp. 1621-1627
The suggested function of cellular retinol-binding protein type I [CRBP(I)I
is to carry retinol to esterifying or oxidizing enzymes. The retinyl ester
s are used in storage or transport, whereas oxidized forms such as all-tran
s or 9-cis retinoic acid are metabolites used in the mechanism of action of
vitamin A. Thus, high expression of human CRBP(I) [hCRBP(I)] in transgenic
mice might be expected to increase the production of retinoic acid in tiss
ues, thereby inducing a phenotype resembling vitamin A toxicity. Alternativ
ely, a vitamin A-deficient phenotype could also be envisioned as a result o
f an increased accumulation of vitamin A in storage cells induced by a high
hCRBP(I) level. Signs of vitamin A toxicity or deficiency were therefore e
xamined in tissues from transgenic mice with ectopic expression of hCRBP(I)
. Testis and intestine, the tissues with the highest expression of the tran
sgene, showed normal gross morphology.: Similarly, no abnormalities were ob
served in other tissues known to be sensitive to vitamin A status such as c
ornea and retina, and the epithelia in the cervix, trachea and-skin. Furthe
rmore, hematologic variables known to be influenced by vitamin A status suc
h as the hemoglobin concentration, hematocrits and the number of red blood
cells were within normal ranges in the transgenic mice. In conclusion, thes
e transgenic mice have normal function of vitamin A despite high expression
of hCRBP(I) in several tissues.