Genomic analysis of the causative gene for the aganglionosis rat and application of this rat to the pharmacological analysis

神经节缺失大鼠致病基因的基因组分析及其在药理分析中的应用

• 批准号: 08680910
• 负责人: AGUI Takashi
• 金额: $ 1.54万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680910/
• 关键词: Hirschsprung's disease; enteric ganglion; endothelin receptor; mutant rat; bone marrow-derived stromal cell; IL-6; VIP; PACAP; 腸管神経節欠損ラット

Expression of endothelin type B receptor (Ednrb) gene in the lung was extremely lower in aganglionosis rats compared to control rats. Further, the size of PCR products of the Ednrb cDNA were shorter in aganglionosis rats compared to that of control rats. By determining the coding sequence of the Ednrb cDNA in aganglionosis rats and comparing it with that of control rats, two kinds of deleted cDNAs were found to be present ; one is deleted between the 20th and 483rd nucleotide and another is deleted between the 213th and 483rd nucleotide. From these results, it is suggested that the cause of aganglionosis is due to a significant decrease in the Ednrb gene expression and deletion of the faintly expressed residual Ednrb mRNA.We tried to examine a role of endothelin in the regulation of IL-6 production in the bone marrow of aganglionosis rats. However, endothelin could not augment IL-6 production by bone marrow-derived stromal cells prepared even from control normal littermates. Thus, it was impossible to examine the effect of endothelin in the bone marrow of this mutant rat. However, we could elucidate that other blood pressure-regulating hormones, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) regulate IL-6 production in the bone marrow.

无神经节细胞症大鼠肺组织内皮素B型受体（Ednr B）基因表达显著低于对照组。此外，与对照大鼠相比，无神经节细胞症大鼠Ednrb cDNA的PCR产物的大小较短。通过测定无神经节细胞症大鼠Ednrb cDNA编码序列并与对照组比较，发现存在两种缺失的cDNA，一种是第20 ~ 483位核苷酸之间的缺失，另一种是第213 ~ 483位核苷酸之间的缺失。从这些结果，这表明，无神经节细胞症的原因是由于Ednrb基因的表达和微弱表达的残留Ednrb mRNA.We试图研究内皮素在调节IL-6产生的无神经节细胞症大鼠骨髓中的作用的显着减少。然而，内皮素不能增加IL-6的生产骨髓来源的基质细胞制备，甚至从控制正常的同窝出生。因此，不可能检查内皮素在这种突变大鼠骨髓中的作用。然而，我们可以阐明，其他血压调节激素，血管活性肠肽（VIP）和垂体腺苷酸环化酶激活多肽（PACAP）调节IL-6在骨髓中的生产。

项目成果

Yiqiang Cai: "Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) stimulate interleukin-6 production through the third subtype of PACAP/VIP receptor in rat bone marrow derived stromal cells" Endocrinology. 13

蔡益强：“垂体腺苷酸环化酶激活多肽（PACAP）和血管活性肠肽（VIP）通过大鼠骨髓来源的基质细胞中 PACAP/VIP 受体的第三种亚型刺激白细胞介素 6 的产生”内分泌学。

G.-J.Shim.: "Abnormal splicing of the endothelin type B receptor mRNA in the aganglionosis rat." Nagoya Med.J.40. 193-201 (1996)

G.-J.Shim.：“神经节缺失大鼠中内皮素 B 型受体 mRNA 的剪接异常。”

Gil-iin Shim: "Abnormal splicing of the endothelin type B receptor mRNA in the aganglionsis rat." Nagoya Med.j.40・4. 193-201 (1996)

Gil-iin Shim：“神经节缺失大鼠中内皮素 B 型受体 mRNA 的异常剪接” Nagoya Med.j.40·4（1996）。

Yiqiang Cai: "Pituitary adenylate cyclase activating polypeptide(PACAP)and vasoactive intestinal peptide(VIP)stimulate interleukin-6 production through the third subtype of PACAP/VIP receptor in rat bone marrow derrved stromal cells" Endocrinology. 1361・6

蔡益强：“垂体腺苷酸环化酶激活多肽（PACAP）和血管活性肠肽（VIP）通过大鼠骨髓基质细胞中 PACAP/VIP 受体的第三亚型刺激白细胞介素 6 的产生”内分泌学 1361・6。

Y.Cai, X.Xin: "Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) stimulate interleukin-6 production through the third subtype of PACAP/VIP receptor in rat bone marrow-derived stromal cells." Endocrinology.

Y.Cai、X.Xin：“垂体腺苷酸环化酶激活多肽 (PACAP) 和血管活性肠肽 (VIP) 通过大鼠骨髓源性基质细胞中 PACAP/VIP 受体的第三种亚型刺激白细胞介素 6 的产生。”