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A genetic dissection of the retinoid signalling pathway in the mouse

Published online by Cambridge University Press:  28 February 2007

Manuel Mark ,
Norbert B. Ghyselinck ,
Olivia Wendling ,
Valérie Dupé ,
Bénédicte Mascrez ,
Philippe Kastner  and
Pierre Chambon
Manuel Mark
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
Norbert B. Ghyselinck
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
Olivia Wendling
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
Valérie Dupé
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
Bénédicte Mascrez
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
Philippe Kastner
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
Pierre Chambon*
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
*
*Corresponding Author: Professor Pierre Chambon, fax +33 38865 3203, email chambon@igbmc.u-strasbg.fr
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Abstract

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To determine the functions of retinoic acid receptors RAR and RXR, we have systematically knocked-out their genes by homologous recombination in the embryonic stem cells and generated null-mutant mice. This approach has allowed us to perform a genetic dissection of the retinoic acid signalling pathway.

Keywords

Retinoic acid receptorsRetinoic acid-binding proteinRetinoic acid signalling pathway
Type
Symposium on ‘Functionality of nutrients and gene expression’
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 3 , August 1999 , pp. 609 - 613
Copyright
Copyright © The Nutrition Society 1999

References

Båvik, C, Ward, SJ & Chambon, P (1996) Developmental abnormalities in cultured mouse embryos deprived of retinoic acid by inhibition of yolk-sac retinol binding protein synthesis. Proceedings of the National Academy of Sciences USA 93, 3110–3114.CrossRefGoogle ScholarPubMed
Chambon, P (1994) The retinoid signaling pathway: molecular and genetic analyses. Seminars in Cell Biology 5, 115–125.Google Scholar
Chambon, P (1996) A decade of molecular biology of retinoic acid receptors. FASEB Journal 10, 940–954.Google Scholar
Dickman, ED, Thaller, C & Smith, SM (1997) Temporally-regulated retinoic acid depletion produces specific neural crest, ocular and nervous system defects. Development 124, 3111–3121.Google Scholar
Dupé, V, Davenne, M, Brocard, J, Dollé, P, Mark, M, Dierich, A, Chambon, P & Rijli, FM (1997) In vivo functional analysis of the. Hoxa-13′ retinoic acid response element (3>RARE). Development 124, 399–410.CrossRefGoogle Scholar
Dupé, V, Ghyselinck, NB, Thomazy, V, Nagy, L, Davies, PJA, Chambon, P & Mark, M (1999) Essential roles of retinoic acid signaling in interdigital apoptosis and control of BMP-7 expression in mouse autopods. Developmental Biology 208, 30–43.CrossRefGoogle ScholarPubMed
Ghyselinck, NB, Dupé, V, Dierich, A, Messaddeq, N, Garnier, JM, Rochette-Egly, C, Chambon, P & Mark, M (1997) Role of retinoic acid receptor beta (RARβ) during mouse development. International Journal of Developmental Biology 41, 425–447.Google ScholarPubMed
Ghyselinck, NB, Wendling, O, Messaddeq, N, Dierich, A, Lampron, C, Décimo, D, Viville, S, Chambon, P & Mark, M (1998) Contribution of retinoic acid receptor beta isoforms to the formation of the conotruncal septum of the embryonic heart. Developmental Biology 198, 303–318.CrossRefGoogle Scholar
Grondona, JM, Kastner, P, Gansmuller, A, Décimo, D, Chambon, P & Mark, M (1996) Retinal dysplasia and degeneration in RARβ2/RARγ2 compound mutant mice. Development 122, 2173–2188.CrossRefGoogle ScholarPubMed
Hale, F (1937) The relation of maternal vitamin A deficiency to microphthalmia in pigs. Texas State Journal of Medicine 33, 228–232.Google Scholar
Kalter, H & Warkany, J (1959) Experimental production of congenital malformations in mammals by metabolic procedure. Physiological Review 39, 69–115.CrossRefGoogle ScholarPubMed
Kastner, P, Grondona, JM, Mark, M, Gansmuller, A, LeMeur, M, Décimo, D, Vonesch, JL, Dollé, P & Chambon, P (1994) Genetic analysis of RXRα developmental function: convergence of RXR and RAR signalling pathways in heart and eye morphogenesis. Cell 78, 987–1003.CrossRefGoogle Scholar
Kastner, P, Mark, M & Chambon, P (1995) Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life? Cell 83, 859–869.CrossRefGoogle ScholarPubMed
Kastner, P, Mark, M, Ghyselinck, NB, Krezel, W, Dupé, V, Grondona, JM & Chambon, P (1997 a) Genetic evidence that the retinoid signal is transduced by heterodimeric RXR/RAR functional units during mouse development. Development 124, 313–326.Google Scholar
Kastner, P, Mark, M, Leid, M, Gansmuller, A, Grondona, JM, Décimo, D, Krezel, W, Dierich, A & Chambon, P (1996) Abnormal spermatogenesis in RXRβ mutant mice. Genes and Development 10, 80–96.CrossRefGoogle Scholar
Kastner, P, Messaddeq, N, Mark, M, Wendling, O, Grondona, JM, Ward, S, Ghyselinck, N & Chambon, P (1997 b) Vitamin A deficiency and mutations of RXRα, RXRβ and RARα lead to early differentiation of embryonic ventricular cardiomyocytes. Development 124, 4749–4758.CrossRefGoogle ScholarPubMed
Krezel, W, Dupé, V, Mark, M, Dierich, A, Kastner, P & Chambon, P (1996) RXRg null mice are apparently normal and compound RXRα+/-/RXRβ-/-/RXRγ-/- mutant mice are viable. Proceedings of the National Academy of Sciences USA 93, 9010–9014.CrossRefGoogle Scholar
Krezel, W, Ghyselinck, N, Samad, TA, Dupé, V, Kastner, P, Borrelli, E & Chambon, P (1998) Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science 279, 863–867.Google Scholar
Lampron, C, Rochette-Egly, C, Gorry, P, Dollé, P, Mark, M, Lufkin, T, LeMeur, M & Chambon, P (1995) Mice deficient in cellular retinoic acid binding protein II (CRABPII) or in both CRABPI and CRABPII are essentially normal. Development 121, 539–548.CrossRefGoogle ScholarPubMed
Lohnes, D, Kastner, P, Dierich, A, Mark, M, LeMeur, M & Chambon, P (1993) Function of retinoic acid receptor gamma in the mouse. Cell 73, 643–658.CrossRefGoogle ScholarPubMed
Lohnes, D, Mark, M, Mendelsohn, C, Dollé, P, Dierich, A, Gorry, P, Gansmuller, A & Chambon, P (1994) Function of the retinoic acid receptors (RARs) during development (1). Craniofacial and skeletal abnormalities in RAR double mutants. Development 120, 2723–2748.CrossRefGoogle Scholar
Lufkin, T, Lohnes, D, Mark, M, Dierich, A, Gorry, P, Gaub, MP, LeMeur, M & Chambon, P (1993) High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proceedings of the National Academy of Sciences USA 90, 7225–7229.CrossRefGoogle ScholarPubMed
Mark, M & Chambon, P (1997) Récepteurs de l’acide rétinoïque et morphogenèse (Retinoic acid receptors and morphogenesis). Annales de l’Institut Pasteur 8, 85–95.CrossRefGoogle Scholar
Mark, M, Ghyselinck, NB, Kastner, P, Dupé, V, Wendling, O, Krezel, W, Mascrez, B & Chambon, P (1998) Mesectoderm is a major target of retinoic acid action. European Journal of Oral Science 106, Suppl.1, 24–31.CrossRefGoogle Scholar
Mark, M, Kastner, P, Ghyselinck, NB, Krezel, W, Dupé, V & Chambon, P (1997) Contrôle génétique du développement par l’acide rétinoïque (Genetic control of development by retinoic acid). Comptes Rendus de la Société de Biologie 191, 77–90.Google ScholarPubMed
Mark, M, Lohnes, D, Mendelsohn, C, Dupé, V, Vonesch, JL, Kastner, P, Rijli, F, Bloch-Zupan, A & Chambon, P (1995) Roles of retinoic acid receptors and of. Hox genes in the patterning of the teeth and of the jaw skeleton. International Journal of Developmental Biology 39, 111–121.Google ScholarPubMed
Mascrez, B, Mark, M, Dierich, A, Ghyselinck, NB, Kastner, P & Chambon, P (1998) The RXRα ligand-dependent activation function 2 (AF-2) is important for mouse development. Development 125, 4691–4707.CrossRefGoogle ScholarPubMed
Mendelsohn, C, Lohnes, D, Décimo, D, Lufkin, T, LeMeur, M, Chambon, P & Mark, M (1994) Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. Development 120, 2749–2771.Google Scholar
Sapin, V, Dollé, P, Hindelang, C, Kastner, P & Chambon, P (1997) Defects of the chorioallantoic placenta in mouse RXRα null fetuses. Developmental Biology 191, 29–41.Google Scholar
Subbarayan, V, Kastner, P, Mark, M, Dierich, A, Gorry, P & Chambon, P (1997) Limited specificity and large overlap of the functions of the mouse RARγ1 and RARγ2 isoforms. Mechanisms in Development 66, 131–142.CrossRefGoogle Scholar
Wendling, O, Chambon, P & Mark, M (1999 a) Retinoid X receptors are essential for early mouse development and placentogenesis. Proceedings of the National Academy of Sciences USA 96, 547–551.CrossRefGoogle ScholarPubMed
Wendling, O, Chambon, P & Mark, M (1999 b) Un rôle essentiel des récepteurs des rétinoïdes au cours du développement embryonnaire précoce et de la placentogenèse (An essential role for retinoid receptors during early embryonic development and placentogenesis). Médecine/Sciences (In the Press).Google Scholar
Wilson, JG, Roth, CB & Warkany, J (1953) An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. American Journal of Anatomy 92, 189–217.CrossRefGoogle ScholarPubMed