Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants.
Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants.
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发表时间：
1994-10
期刊：
影响因子：
4.6
通讯作者：
C. Mendelsohn;D. Lohnes;D. Décimo;T. Lufkin;M. Lemeur;P. Chambon;M. Mark
中科院分区：
文献类型：
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作者：
C. Mendelsohn;D. Lohnes;D. Décimo;T. Lufkin;M. Lemeur;P. Chambon;M. Mark
维甲酸受体（RAR）基因的复合无效突变导致子宫内或出生后不久的致死性和许多发育异常。在随附的论文中（Lohnes，D.，马克，M.，Mendelsohn，C.，Dollé，P.，Dierich，A.，戈里博士，Gansmuller，A. Chambon，P.（1994）. Development 120，2723-2748），我们描述了头部、椎骨和四肢的畸形，除了眼睛缺陷之外，在维生素A缺乏（VAD）母鼠的后代中没有观察到这些畸形。我们在这里报告异常的颈部，躯干和腹部区域的RAR双突变小鼠，其中包括：（i）整个呼吸道，（ii）心脏，其outlow道和大血管位于心脏附近，（iii）胸腺，甲状腺和甲状旁腺，（iv）隔膜，（v）生殖泌尿系统，（vi）下消化道。这些异常中的大多数概括了40多年前Joseph Warkany小组描述的胎儿VAD综合征中观察到的那些[Wilson，J.G.，罗斯角B。和Warkany，J.（1953）Am. J. Anat.，189.第189章：你是谁？我们的研究结果清楚地表明，RAR是脊椎动物个体发育所必需的，因此，视黄酸是活性类维生素A，这是需要在许多组织和器官的发展的几个阶段。我们讨论了几种可能性，可能占视黄酸受体在胚胎发生过程中观察到的明显的功能冗余。
Compound null mutations of retinoic acid receptor (RAR) genes lead to lethality in utero or shortly after birth and to numerous developmental abnormalities. In the accompanying paper (Lohnes, D., Mark., M., Mendelsohn, C., Dollé, P., Dierich, A., Gorry, Ph., Gansmuller, A. and Chambon, P. (1994). Development 120, 2723-2748), we describe malformations of the head, vertebrae and limbs which, with the notable exception of the eye defects, were not observed in the offspring of vitamin A-deficient (VAD) dams. We report here abnormalities in the neck, trunk and abdominal regions of RAR double mutant mice, which include: (i) the entire respiratory tract, (ii) the heart, its outlow tract and the great vessels located near the heart, (iii) the thymus, thyroid and parathyroid glands, (iv) the diaphragm, (v) the genito-urinary system, and (vi) the lower digestive tract. A majority of these abnormalities recapitulate those observed in the fetal VAD syndrome described by Joseph Warkany's group more than fourty years ago [Wilson, J. G., Roth, C. B. and Warkany, J. (1953) Am. J. Anat., 92, 189-217; and refs therein]. Our results clearly demonstrate that RARs are essential for vertebrate ontogenesis and therefore that retinoic acid is the active retinoid, which is required at several stages of the development of numerous tissues and organs. We discuss several possibilities that may account for the apparent functional redundancy observed amongst retinoic acid receptors during embryogenesis.