Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein

被引:385
作者
Quadro, L
Blaner, WS
Salchow, DJ
Vogel, S
Piantedosi, R
Gouras, P
Freeman, S
Cosma, MP
Colantuoni, V
Gottesman, ME
机构
[1] Columbia Univ Coll Phys & Surg, Inst Canc Res, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Dept Ophthalmol, New York, NY 10032 USA
[4] Univ Naples, Dept Biochem & Med Biotechnol, I-80131 Naples, Italy
关键词
electroretinogram; high performance liquid chromatography; knockout mice; retinol-binding protein; vitamin A;
D O I
10.1093/emboj/18.17.4633
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Retinol-binding protein (RBP) is the sole specific transport protein for retinol (vitamin A) in the circulation, and its single known function is to deliver retinol to tissues. Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of >300 diverse target genes. In the eye, retinol is also activated to 11-cis-retinal, the visual chromophore, We generated REP knockout mice (RBP-/-) by gene targeting. These mice have several phenotypes. Although viable and fertile, they have reduced blood retinol levels and markedly impaired retinal function during the first months of life. The impairment is not due to developmental retinal defect. Given a vitamin A-sufficient diet, the RBP-/- mice acquire normal vision by 5 months of age even though blood retinol levels remain low, Deprived of dietary vitamin A, vision remains abnormal and blood retinol declines to undetectable levels. Another striking phenotype of the mutant mice is their abnormal retinol metabolism. The RBP-/- mice can acquire hepatic retinol stores, but these cannot be mobilized. Thus, their vitamin A status is extremely tenuous and dependent on a regular vitamin A intake, Unlike wild-type mice, serum retinol levels in adult RBP-/- animals become undetectable after only a week on a vitamin A-deficient diet and their retinal function rapidly deteriorates, Thus REP is needed for normal vision in young animals and for retinol mobilization in times of insufficient dietary intake, but is otherwise dispensable for the delivery of retinol to tissues.
引用
收藏
页码:4633 / 4644
页数:12
相关论文
共 53 条
  • [1] Barron M, 1998, DEV DYNAM, V212, P413, DOI 10.1002/(SICI)1097-0177(199807)212:3<413::AID-AJA9>3.0.CO
  • [2] 2-K
  • [3] Developmental abnormalities in cultured mouse embryos deprived of retinoic acid by inhibition of yolk-sac retinol binding protein synthesis
    Bavik, C
    Ward, SJ
    Chambon, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) : 3110 - 3114
  • [4] BAVIK CO, 1993, J BIOL CHEM, V268, P20540
  • [5] How photons start vision
    Baylor, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) : 560 - 565
  • [6] Mice deficient in Golf are anosmic
    Belluscio, L
    Gold, GH
    Nemes, A
    Axel, R
    [J]. NEURON, 1998, 20 (01) : 69 - 81
  • [7] Biesalski HK, 1999, AM J CLIN NUTR, V69, P931
  • [8] Blaner William S., 1994, P229
  • [9] BLANER WS, 1987, J BIOL CHEM, V262, P53
  • [10] BLANER WS, 1990, METHOD ENZYMOL, V189, P270