Lohnes D, Mark M, Mendelsohn C, Dollé P, Dierich A, Gorry P, Gansmuller A, Chambon P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Development. 1994 Oct;120(10):2723-48. doi: 10.1242/dev.120.10.2723.
Numerous congenital malformations have been observed in fetuses of vitamin A-deficient (VAD) dams [Wilson, J. G., Roth, C. B., Warkany, J., (1953), Am. J. Anat. 92, 189-217]. Previous studies of retinoic acid receptor (RAR) mutant mice have not revealed any of these malformations [Li, E., Sucov, H. M., Lee, K.-F., Evans, R. M., Jaenisch, R. (1993) Proc. Natl. Acad. Sci. USA 90, 1590-1594; Lohnes, D., Kastner, P., Dierich, A., Mark, M., LeMeur, M., Chambon, P. (1993) Cell 73, 643-658; Lufkin, T., Lohnes, D., Mark, M., Dierich, A., Gorry, P., Gaub, M. P., Lemeur, M., Chambon, P. (1993) Proc. Natl. Acad. Sci. USA 90, 7225-7229; Mendelsohn, C., Mark, M., Dollé, P., Dierich, A., Gaub, M.P., Krust, A., Lampron, C., Chambon, P. (1994a) Dev. Biol. in press], suggesting either that there is a considerable functional redundancy among members of the RAR family during ontogenesis or that the RARs are not essential transducers of the retinoid signal in vivo. In order to discriminate between these possibilities, we have generated a series of RAR compound null mutants. These RAR double mutants invariably died either in utero or shortly after birth and presented a number of congenital abnormalities, which are reported in this and in the accompanying study. We describe here multiple eye abnormalities which are found in various RAR double mutant fetuses and are similar to those previously seen in VAD fetuses. Interestingly, we found further abnormalities not previously reported in VAD fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)
在维生素A缺乏（VAD）的母鼠所产胎儿中已观察到众多先天性畸形[威尔逊，J.G.，罗斯，C.B.，瓦尔卡尼，J.，（1953年），《美国解剖学杂志》92卷，第189 - 217页]。先前对视黄酸受体（RAR）突变小鼠的研究未发现这些畸形中的任何一种[李，E.，苏科夫，H.M.，李，K.-F.，埃文斯，R.M.，杰尼施，R.（1993年）《美国国家科学院院刊》90卷，第1590 - 1594页；洛内斯，D.，卡斯特纳，P.，迪里希，A.，马克，M.，勒梅尔，M.，尚邦，P.（1993年）《细胞》73卷，第643 - 658页；卢夫金，T.，洛内斯，D.，马克，M.，迪里希，A.，戈里，P.，高布，M.P.，勒梅尔，M.，尚邦，P.（1993年）《美国国家科学院院刊》90卷，第7225 - 7229页；门德尔松，C.，马克，M.，多勒，P.，迪里希，A.，高布，M.P.，克鲁斯特，A.，兰普龙，C.，尚邦，P.（1994年a）《发育生物学》待发表]，这表明要么在个体发育过程中RAR家族成员之间存在相当程度的功能冗余，要么RAR在体内并非视黄酸信号的必需转导因子。为了区分这些可能性，我们构建了一系列RAR复合无效突变体。这些RAR双突变体总是在子宫内或出生后不久死亡，并呈现出许多先天性异常，本研究及相关研究对此进行了报道。我们在此描述了在各种RAR双突变胎儿中发现的多种眼部异常，这些异常与先前在VAD胎儿中所见的相似。有趣的是，我们还发现了VAD胎儿中先前未报道过的其他异常。（摘要截短至250字）
