Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Chem Biol Interact. 2019 Apr 1;302:117-122. doi: 10.1016/j.cbi.2019.01.041. Epub 2019 Feb 4.
Retinol dehydrogenase 11 (RDH11) is an NADPH-dependent retinaldehyde reductase that was previously reported to function in the visual cycle. Recently, we have shown that RDH11 contributes to the maintenance of retinol levels in extraocular tissues under conditions of vitamin A deficiency or reduced vitamin A availability. RDH11 is also expressed in the embryo. Rdh11 knockout animals do not display embryonic defects and appear to develop normally to the adult stage, but the exact function of RDH11 during development is not yet known. In contrast to RDH11-null mice, animals that lack dehydrogenase/reductase 3 (DHRS3), the enzyme that functions as a retinaldehyde reductase and is essential for the maintenance of retinoid homeostasis during embryogenesis, rarely survive until birth. Here, we investigated whether inactivation of RDH11 together with DHRS3 exacerbates the severity of retinoid homeostasis disruption in embryos that lack both enzymes compared to DHRS3-null mice. The results of this study indicate that in vitamin A sufficient animals, the loss of RDH11 in addition to DHRS3 does not appear to significantly impact the total levels of retinoic acid, free retinol, or retinyl esters in Rdh11/Dhrs3embryos in comparison to Dhrs3 embryos. Surprisingly, Rdh11 single gene knockout embryos obtained from breeding of Rdh11 dams display elevated levels of embryonic retinyl esters compared to wild type embryos. The mechanism of the maternal effect of Rdh11 status on fetal retinoid stores remains to be elucidated.
视黄醛脱氢酶 11（RDH11）是一种 NADPH 依赖性视黄醛还原酶，先前报道其在视觉循环中发挥作用。最近，我们表明，在维生素 A 缺乏或维生素 A 可用性降低的情况下，RDH11 有助于维持眼外组织中的视黄醇水平。RDH11 也在胚胎中表达。Rdh11 基因敲除动物不会显示胚胎缺陷，似乎正常发育到成年阶段，但 RDH11 在发育过程中的确切功能尚不清楚。与 RDH11 基因敲除小鼠不同，缺乏脱氢酶/还原酶 3（DHRS3）的动物很少能存活到出生，DHRS3 是一种作为视黄醛还原酶发挥作用的酶，对于胚胎发生期间类视黄醇稳态的维持是必不可少的。在这里，我们研究了与 DHRS3 基因敲除小鼠相比，RDH11 与 DHRS3 同时失活是否会加剧缺乏这两种酶的胚胎中类视黄醇稳态破坏的严重程度。这项研究的结果表明，在维生素 A 充足的动物中，与 DHRS3 基因敲除小鼠相比，除了 DHRS3 之外，RDH11 的缺失似乎不会显著影响 Rdh11/Dhrs3 胚胎中视黄酸、游离视黄醇或视黄基酯的总水平。令人惊讶的是，与野生型胚胎相比，从 Rdh11 母鼠繁殖获得的 Rdh11 单基因敲除胚胎中的胚胎视黄基酯水平升高。Rdh11 状态对胎儿类视黄醇储存的母体效应的机制仍有待阐明。
