Deficiency of WFS1 leads to the impairment of AVP secretion under dehydration in male mice.
Deficiency of WFS1 leads to the impairment of AVP secretion under dehydration in male mice.
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WFS1 缺陷会导致雄性小鼠在脱水情况下 AVP 分泌受损。
DOI：
10.1007/s11102-021-01135-6
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发表时间：
2021
期刊：
影响因子：
3.8
通讯作者：
Arima H.
中科院分区：
文献类型：
--
作者：
Kurimoto J;Takagi H;Miyata T;Hodai Y;Kawaguchi Y;Hagiwara D;Suga H;Kobayashi T;Sugiyama M;Onoue T;Ito Y;Iwama S;Banno R;Tanabe K;Tanizawa Y;Arima H.
Wolfram综合征（WS）主要由WFS 1基因突变引起，以糖尿病、视神经萎缩、听力丧失和中枢性尿崩症（CDI）为特征。WFS 1是一种内质网（ER）驻留跨膜蛋白，据报道，Wfs 1敲除（Wfs 1-/-）小鼠已被用作WS的小鼠模型，表现出由于胰腺β细胞丢失而导致的葡萄糖耐量受损。在本研究中，我们研究了水平衡，精氨酸加压素（AVP）的分泌，和ER应激的AVP神经元的下丘脑在Wfs 1-/-小鼠。在自由饮水的情况下，Wfs 1 −/−和野生型小鼠的尿量没有差异。相反，当小鼠间歇性缺水（WD）20周时，在此期间每周有2天没有水，与野生型小鼠相比，Wfs 1 −/−小鼠的尿量较大，伴随着较低的尿液AVP浓度和尿液渗透压。免疫球蛋白重链结合蛋白（ER应激的标志物）的mRNA表达在WD后Wfs 1 −/−小鼠的视上核和室旁核中显著增加。因此，我们的研究结果表明，Wfs 1基因敲除导致脱水时AVP分泌减少，这可以部分解释Wfs 1突变导致人类CDI的机制。
Wolfram syndrome (WS) is mainly caused by mutations in theWFS1gene and characterized by diabetes mellitus, optic atrophy, hearing loss, and central diabetes insipidus (CDI). WFS1 is an endoplasmic reticulum (ER)-resident transmembrane protein, andWfs1knockout (Wfs1−/−) mice, which have been used as a mouse model for WS, reportedly manifested impairment of glucose tolerance due to pancreatic β-cell loss. In the present study, we examined water balance, arginine vasopressin (AVP) secretion, and ER stress in AVP neurons of the hypothalamus inWfs1−/− mice. There were no differences in urine volumes betweenWfs1−/− and wild-type mice with free access to water. Conversely, when mice were subjected to intermittent water deprivation (WD) for 20 weeks, during which water was unavailable for 2 days a week, urine volumes were larger inWfs1−/− mice, accompanied by lower urine AVP concentrations and urine osmolality, compared to wild-type mice. The mRNA expression of immunoglobulin heavy chain binding protein, a marker of ER stress, was significantly increased in the supraoptic nucleus and paraventricular nuclei inWfs1−/− mice compared to wild-type mice after WD. Our results thus showed thatWfs1knockout leads to a decrease in AVP secretion during dehydration, which could explain in part the mechanisms by whichWfs1mutations cause CDI in humans.