The genetic role of retinoic acid receptors in embryonic development: Study of genetic mutations in retinoic acid receptors, resulting in tissue abnormalities
Retinoic acid (RA) is a vitamin A derivative that exerts profound influences in vertebrate development and physiology. All-trans RA and 9-cis RA, are important regulators of embryonic development, cellular activity and tissue homeostasis. Their biological effects are mediated by two families of nuclear hormone receptors, retinoic acid (RAR) and retinoid X (RXR) receptors, which are ligand-dependent transcription factor. In the form of RAR-RXR or RXR-RXR dimers, the receptors act through binding to retinoic acid response elements (RAREs) present in the transcription regulatory region (promoter) of target genes. The identification of the pattern of expression of each isoform is crucial to our complete understanding of retinoid physiology. Compound null mutations of retinoic acid receptor (RAR) genes lead to lethality in uterus or shortly after birth and to numerous developmental abnormalities. The role of RXRs in the mediation of the developmental retinoid signal is less clear, because RXRβ and RXRγ null mutant mice are viable and do not display any abnormality obviously related to a known function of vitamin A. Effects of retinoids in normal as well as abnormal development may be mediated by two members of retinoid receptors together, RARs and RXRs.
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