GENETIC-ANALYSIS OF RXR-ALPHA, DEVELOPMENTAL FUNCTION - CONVERGENCE OF RXR AND RAR SIGNALING PATHWAYS IN HEART AND EYE MORPHOGENESIS

被引：592

作者：

KASTNER, P

GRONDONA, JM

MARK, M

GANSMULLER, A

LEMEUR, M

DECIMO, D

VONESCH, JL

DOLLE, P

CHAMBON, P

机构：

[1] Laboratoire de Génétique Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique, Institut de Chimie Biologique Faculté de Médecine, 67085 Strasbourg Cédex, 11, rue Humann

[2] Unité 184 de Biologie Moléculaire et de Génie Génétique, l'Institut National de la Santé, la Recherche Médicale Institut, 67085 Strasbourg Cédex, 11, rue Humann

来源：

CELL | 1994年 / 78卷 / 06期

关键词：

D O I：

10.1016/0092-8674(94)90274-7

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：

A null mutation was generated in the mouse RXR alpha gene by targeted disruption. Growth deficiency occurred in heterozygote mice. Null mutants died in utero and displayed myocardial and ocular malformations. These malformations belong to the fetal vitamin A deficiency syndrome, supporting the idea that RXR alpha is involved in retinoid signaling in vivo. A phenotypic synergy was observed when the RXR alpha mutation was introduced into RAR alpha or RAR gamma mutant backgrounds: RXR alpha null mutants and RXR alpha(+/-)/RAR gamma(-/-) double mutants displayed similar ocular defects, which became more severe in RXR alpha(-/-)/RAR gamma(+/-) and RXR alpha(-/-)/RAR gamma(-/-) mutants. Furthermore, RXR alpha/RAR double mutants exhibited several malformations not seen in single mutants. This functional convergence strongly suggests that RXR alpha/RAR heterodimers mediate retinoid signaling in vivo.

引用

页码：987 / 1003

页数：17

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