HIGH POSTNATAL LETHALITY AND TESTIS DEGENERATION IN RETINOIC ACID RECEPTOR-ALPHA MUTANT MICE
HIGH POSTNATAL LETHALITY AND TESTIS DEGENERATION IN RETINOIC ACID RECEPTOR-ALPHA MUTANT MICE
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DOI：
10.1073/pnas.90.15.7225
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发表时间：
1993-08-01
影响因子：
11.1
通讯作者：
CHAMBON, P
中科院分区：
文献类型：
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作者：
LUFKIN, T;LOHNES, D;CHAMBON, P
维甲酸(RA)在某些组织的正常发育、生长和维持中起着关键作用。RA的作用被认为部分是由三种核受体(RARα、-β和-γ)介导的，每种受体都以多种异构体的形式表达。为了研究RARAlpha基因的功能，我们在小鼠中干扰了整个基因或RARalpha1的异构体。虽然RARalpha1是主要的亚型，在脊椎动物中高度保守，但RARalpha1缺失的小鼠看起来是正常的。然而，靶向破坏整个RARpha基因会导致出生后早期死亡和睾丸退化。这些结果表明，RARpha确实参与了RA信号的转导，也表明了一种意想不到的基因冗余。
Retinoic acid (RA) plays a critical role in normal development, growth, and maintenance of certain tissues. The action of RA is thought to be mediated in part by the three nuclear receptors (RARalpha, -beta, and -gamma), each of which is expressed as multiple isoforms. To investigate the function of the RARalpha gene, we have disrupted, in the mouse, the whole gene or the isoform RARalpha1. Although RARalpha1 is the predominant isoform and is highly conserved among vertebrates, RARalpha1-null mice appeared normal. However, targeted disruption of the whole RARalpha gene resulted in early postnatal lethality and testis degeneration. These results, showing that RARalpha is indeed involved in the transduction of the RA signal, also suggest an unexpected genetic redundancy.