Research for the causative genes of the congenital abnormality using analysis of the action points of teratogenic factors

通过致畸因素作用点分析研究先天性畸形的致病基因

• 批准号: 12670747
• 负责人: SAKAI Norio
• 金额: $ 2.5万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670747/
• 关键词: congenital defects; teratogenic factor; deformity

It is believed that more than half of the congenital defects is caused with the interaction between genetic factors and circumstance factors. In this report, we analyzed the new method how to approach the action mechanism of the circumstance factors.In last two years, 1) we screened the target genes of the overexpressed gene in the cultured cells with gene trap method and analyzed their in vivo expression pattern, 2) we screened the causative genes of the inherited diseases including vertebrate deformity.1) We used ES cells and ATDC5 cell line, progenitor of chondrocyte, for the screening of target genes of Pax1/9. We detected two genes, Pumilio and Siena, as candidate target gene. These genes are analyzed expression pattern in both of normal and mutant mouse embryos, in order to detect the regulation of transcription.2) Two patients diagnosed as Jarcho-Levin syndrome are analyzed in its causative gene, Dll-3, which is in progress. The patient suspected as Schwarz-Jampel syndrome is analyzed in Pumilio gene, which is found to be mapped to critical region of this disease, however, it is proved that this disease is caused with the mutation of Perlecan in 2000.

据认为，超过一半的先天缺陷是由遗传因素和环境因素相互作用造成的。本研究分析了探讨环境因素作用机制的新方法，在过去的两年中，我们1）用基因陷阱法筛选培养细胞中过表达基因的靶基因，并分析其在体内的表达模式; 2）筛选遗传性疾病（包括脊椎动物畸形）的致病基因。1）我们利用ES细胞和ATDC 5细胞系，软骨细胞的祖细胞，用于筛选Pax 1/9的靶基因。我们检测到Pumilio和Siena两个基因作为候选靶基因。分析这些基因在正常和突变小鼠胚胎中的表达模式，以检测转录的调节。2）分析两名诊断为Jarcho-Levin综合征的患者的致病基因Dll-3，该基因正在进行中。对疑似Schwarz-Jampel综合征患者进行Pumilio基因分析，发现Pumilio基因定位于该病的关键区域，但2000年证实该病是由Perlecan突变引起的。

项目成果

Tsukamoto H, Yamamoto T, Nishigaki T, Sakai N, Inui K et al.: "SSCP analysis by RT-PCR for the prenatal diagnosis of Niemann-Pick disease type C"Prenat Diagn.. 21. 55-57 (2001)

Tsukamoto H、Yamamoto T、Nishigaki T、Sakai N、Inui K 等人：“通过 RT-PCR 进行 SSCP 分析用于 Niemann-Pick 病 C 型产前诊断”Prenat Diagn.. 21. 55-57 (2001)

Akagi M, Inul K, Tsukamoto H, Sakai N, et al.: "A point mutation of mitochondria ATPase 6 gene in Leigh syndrome"Neuromuscul Disord. et al.. 12. 53-55 (2002)

Akagi M、Inul K、Tsukamoto H、Sakai N 等：“Leigh 综合征中线粒体 ATP 酶 6 基因的点突变”神经肌肉疾病。

Tsukamoto H, Yamamoto, Nishigaki T, Sakai N, Inui K et al.: "SSCP analysis by RT-PCR for the prenatal diagnosis of Niemann-Pick disease type C"Prenat Diagn.. 21. 55-57 (2001)

Tsukamoto H、Yamamoto、Nishigaki T、Sakai N、Inui K 等人：“通过 RT-PCR 进行 SSCP 分析用于 Niemann-Pick 病 C 型产前诊断”Prenat Diagn.. 21. 55-57 (2001)

Akagi M, Inui K, Tsukamoto H, Sakai N, Muramatsu T, Yamada M, Matsuzaki K, Goto Y, Nonaka I, Okada S.: "A point mutation of mitochondrial ATPase 6 gene in Leigh syndrome"Neuromuscul Disord. 12. 53-5 (2002)

Akagi M、Inui K、Tsukamoto H、Sakai N、Muramatsu T、Yamada M、Matsuzaki K、Goto Y、Nonaka I、Okada S.：“Leigh 综合征中线粒体 ATP 酶 6 基因的点突变”神经肌肉疾病。

Inui k et al: "A case of chronic infantile type of fucosidosis: clinical and magnetic resonance image findings"Brain Dev. 22. 47-49 (2000)

Inui k 等人：“慢性婴儿型岩藻糖苷沉积症的一例：临床和磁共振图像发现”Brain Dev。