Marked resistance of RARgamma-deficient mice to the toxic effects of retinoic acid
1995
Look, J. | Landwehr, J. | Bauer, F. | Hoffmann, A.S. | Bluethmann, H. | Lemotte, P.
Excessive intake of retinol or of retinoic acid causes a syndrome of characteristic toxic effects known as hypervitaminosis A. To test the role of the nuclear retinoic acid receptor (RARgamma) in this process we produced mice with a targeted disruption of the RARgamma gene and examined toxic effects of repeated doses of retinoic acid and two other synthetic retinoids, Ro 15-1570 and Ro 40-6055. Surprisingly, homozygous mutant mice were resistant to fourfold higher doses of retinoic acid than wild-type mice as well as to elevated doses of the synthetic retinoids, indicating that RARgamma may have a major role in mediating retinoid toxicity, a finding that possibly has practical implications for reducing the toxicity of synthetic retinoids in clinical use.
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