NORADRENALINE IS ESSENTIAL FOR MOUSE FETAL DEVELOPMENT
NORADRENALINE IS ESSENTIAL FOR MOUSE FETAL DEVELOPMENT
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DOI：
10.1038/374643a0
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发表时间：
1995-04-13
期刊：
影响因子：
64.8
通讯作者：
PALMITER, RD
中科院分区：
文献类型：
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作者：
THOMAS, SA;MATSUMOTO, AM;PALMITER, RD
儿茶酚胺，如去甲肾上腺素和肾上腺素与许多生理过程有关（1-4），但是，尽管儿茶酚胺的合成始于妊娠中期(5)，以前的研究几乎没有证据表明儿茶酚胺在早期发育中有任何作用（6,7）。此外，也有一些人类去甲肾上腺素缺乏的病例报告(8)。为了研究这一点，我们使用基因靶向(9)来制造缺乏多巴胺β -羟化酶的小鼠，因此无法合成去甲肾上腺素或肾上腺素。我们在这里报道，在杂合子母亲中，大多数纯合子胚胎在子宫内死亡，只有约5%的胚胎能发育成成年。存活可能取决于儿茶酚胺在胎盘中的转移，因为在纯合子母亲中，所有胚胎都在子宫内死亡。死亡是由于在子宫内缺乏去甲肾上腺素，因为它可以通过用二羟基苯基丝氨酸治疗来预防，二羟基苯基丝氨酸是一种前体，在缺乏多巴胺-羟化酶的情况下可以转化为去甲肾上腺素。突变胚胎的组织学表型与酪氨酸羟化酶缺乏的胚胎相似（10），表明死亡可能是由于心血管衰竭。
CATECHOLAMINES such as noradrenaline and adrenaline have been implicated in numerous physiological processes(1-4) but, although catecholamine synthesis begins at mid-gestation(5), previous studies have provided little evidence for any role in early development(6,7). Furthermore, there are several case reports of humans with noradrenaline deficiency(8). To investigate this, we used gene targeting(9) to produce mice lacking dopamine beta-hydroxylase and therefore unable to synthesize noradrenaline or adrenaline. We report here that in heterozygous mothers, most homozygous embryos died in utero, and only about 5% reached adulthood. Survival probably depends on catecholamine transfer across the placenta because, in homozygous mothers, all embryos die in utero. Mortality was due to lack of noradrenaline in utero because it could be prevented by treatment with dihydroxyphenylserine, a precursor that can be converted to noradrenaline in the absence of dopamine beta-hydroxylase. Mutant embryos had a histological phenotype similar to that of embryos deficient in tyrosine hydroxylase(10), suggesting that death might be due to cardiovascular failure.