Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Cell. 1993 May 21;73(4):643-58. doi: 10.1016/0092-8674(93)90246-m.
Null mutant mice for retinoic acid receptor gamma 2 (RAR gamma 2) or all RAR gamma isoforms were generated. RAR gamma 2 mutants appeared normal, whereas RAR gamma mutants exhibited growth deficiency, early lethality, and male sterility due to squamous metaplasia of the seminal vesicles and prostate. These defects were previously observed in vitamin A-deficient animals and could be prevented by RA administration, demonstrating that RAR gamma mediates some of the retinoid signal in vivo. Congenital defects included Harderian gland agenesis, tracheal cartilage malformations, and homeotic transformations along the rostral axial skeleton, establishing a direct link between RA and patterning of the axial skeleton. We also show that in utero RA-induced lumbosacral truncations are mediated by RAR gamma. The observed RAR gamma null phenotype suggests a high degree of functional redundancy among the RARs. The variable penetrance of some of the observed defects is discussed in light of this redundancy and stochastic variation of gene activity.
生成了视黄酸受体γ2（RARγ2）或所有RARγ亚型的基因敲除小鼠。RARγ2突变体看起来正常，而RARγ突变体由于精囊和前列腺的鳞状化生而表现出生长缺陷、早期致死率和雄性不育。这些缺陷先前在维生素A缺乏的动物中观察到，并且可以通过给予视黄酸（RA）来预防，这表明RARγ在体内介导了一些类视黄醇信号。先天性缺陷包括哈德氏腺发育不全、气管软骨畸形以及沿头侧轴向骨骼的同源异型转化，从而在RA与轴向骨骼的模式形成之间建立了直接联系。我们还表明，子宫内RA诱导的腰骶部截断是由RARγ介导的。观察到的RARγ基因敲除表型表明RARs之间存在高度的功能冗余。根据这种冗余和基因活性的随机变化，讨论了一些观察到的缺陷的可变外显率。
