Genetic abnormalities of vasopressin gene and evaluation of gene expression.

加压素基因的遗传异常和基因表达的评估。

• 批准号: 06671019
• 负责人: OISO Yutaka
• 金额: $ 1.34万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671019/
• 关键词: vasopressin gene; gene mutation; familial diabetes insipidus; neurophysin; conformational change; impaired posttranslational processing; プロセシング障害; 分子生物学

Familial central diabetes insipidus (FDI) is an autosomal dominant disease caused by a deficiency of arginine vasopressin (AVP). We have previously reported 6 distinct mutations within the AVP gene encoding the AVP precursor in Japanese patients with FDI in the signal peptide region (A-1T), and the neurophysin region (E47del, G57S,G62W,G65V,C67stop). To study the pathogenesis of FDI,mouse corticotroph AtT20 cells were transfected with either wild-type or mutant human AVP cDNA.Transient transfection studies showed that the AVP immunoreactivity in culture media from cells transfected with each mutant AVP cDNA was markedly decreased compared to wild type (2 to 30%). In patients with AVP gene heterozygosity, one would expect AVP production from the normal allele to be sufficient in preventing diabetes insipidus. However, the disease manifests itself in an autosomal dominant manner. This suggestes that mutant AVP gene products may affect AVP secretion from the wild-type precursor. The potential dominant negative effect was examined in cotransfection experiments. However, the AVP immunoactivity in media obtained from AtT20 cells transiently co-transfected with wild-type and mutant AVP cDNAs was not altered. Further studies will be necessary to explain the sutosomal dominant nature of this disease.

家族性中枢性尿崩症（Familial central diabetes insipidus，FDI）是一种由精氨酸加压素（arginine vasopressin，AVP）缺乏引起的常染色体显性遗传疾病。我们以前曾报道过在日本FDI患者中编码AVP前体的AVP基因内的信号肽区（A-1 T）和neurophysin区（E47 del，G57 S，G62 W，G65 V，C67 stop）的6种不同突变。为研究FDI的发病机制，将野生型和突变型人AVP cDNA分别转染小鼠AtT 20细胞，瞬时转染研究表明，与野生型相比，突变型人AVP cDNA转染的细胞培养液中AVP免疫反应性显著降低（2 ~ 30%）。在具有AVP基因杂合性的患者中，可以预期正常等位基因产生的AVP足以预防尿崩症。然而，该疾病以常染色体显性方式表现出来。这表明突变的AVP基因产物可能影响野生型前体的AVP分泌。在共转染实验中检查了潜在的显性负效应。然而，从AtT 20细胞瞬时共转染野生型和突变体AVP cDNA的培养基中获得的AVP免疫活性没有改变。进一步的研究将是必要的，以解释这种疾病的sutosomal显性的性质。

项目成果

Yutaka Oiso et al.: "The Pituitary Gland,Second Edition," Raven Press,Ltd.,New York,1994, 13 (1994)

Yutaka Oiso 等：“垂体，第二版”，Raven Press, Ltd.，纽约，1994 年，13 (1994)

大磯ユタカ: "最近注目されている神経内分泌疾患:遺伝性尿崩症" ホルモンと臨床. 42. 1031-1036 (1994)

Yutaka Oiso：“最近引起关注的神经内分泌疾病：遗传性尿崩症”激素和临床研究 42. 1031-1036 (1994)。

Hiromitsu Yuasa et al.: "Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus." J.Clin.Endocrinol.Metab.79. 361-365 (1994)

Hiromitsu Yuasa 等人：“两个先天性肾性尿崩症家系中 V2 加压素受体基因的新突变。”

Takashi Murase et al.: "The expression of pituitary adenylate cyclase-activating polypeptide(PACAP)mRNA in rat brain:possible role of endogenous PACAP in vasopressin release." Neuroscience Letters. 185. 103-106 (1995)

Takashi Murase 等人：“大鼠脑中垂体腺苷酸环化酶激活多肽 (PACAP) mRNA 的表达：内源性 PACAP 在加压素释放中的可能作用。”

Hiromitsu Yuasa et al.: "Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus." J.Clin.Endocrional.Metab.79. 361-365 (1994)

Hiromitsu Yuasa 等人：“两个先天性肾性尿崩症家系中 V2 加压素受体基因的新突变。”