Generation of ES cells that stably its translocation to mouse chromosome

产生稳定易位至小鼠染色体的 ES 细胞

• 批准号: 12672200
• 负责人: OSHIMURA Mitsuo
• 金额: $ 1.73万
• 依托单位: Tottori 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-12672200/
• 关键词: Chromosome 10; TC mouse; Chromosome stability; Translocation; DT40; Targeting; Cre-LoxP

To investigate the gene dosage effects of an extra copy of human chromosome on various phenotypes and the regulatory mechanism, we translocated to the distal region of mChr. 10 by a combination of Cre/loxP mediated chromosome translocation and telomere directed chromosome truncation in embryonic stem (ES) cells and homologous recombination proficient DT40 cells. We are, for example, producing chimeric mice that maintain the DCR form the ES cells. These mice should allow stable maintenance in various tissue and stable germline transmission of the DCR (Down syndrome Critical Region). Furthermore, these ES cells will allow mapping and identification of the genes responsible for various phenotype.

为了研究额外拷贝的人类染色体对各种表型的基因剂量效应及其调控机制，我们将其易位到mChr的远端区域。10通过Cre/loxP介导的染色体易位和端粒指导的染色体截短的组合在胚胎干（ES）细胞和同源重组熟练的DT 40细胞中进行。例如，我们正在生产嵌合小鼠，这些小鼠保持来自ES细胞的DCR。这些小鼠应允许在各种组织中稳定维持和DCR（唐氏综合征关键区域）的稳定种系传递。此外，这些ES细胞将允许定位和鉴定负责各种表型的基因。

项目成果

Shinohara, T., Tomizuka, K., Miyabara, S., Takehara, S., Kazuki, Y., Inoue, J., Katoh, M., Nakane, H., Iino, A., Ohguma, A., Ikegami, S., Inokuchi, K., Ishida, I., Reeves, R.H. and Oshimura, M.: "Mice containing a human chromosome 21 model behavioral impa

筱原 T.、富冢 K.、宫原 S.、竹原 S.、一树 Y.、井上 J.、加藤 M.、中根 H.、饭野 A.、大熊 A.、

Shinohara,T., et al.: "Stability of human chromosome fragments in cultured cells and in mice"Chrom.Res.. 8. 713-725 (2000)

Shinohara,T., et al.：“培养细胞和小鼠中人类染色体片段的稳定性”Chrom.Res.. 8. 713-725 (2000)

Kazuki, Y., et al.: "Germline transmission of a transferred human chromosome 21 fragment in transchromosomal mice"J. Hum. Genet.. 46. 600-603 (2001)

Kazuki, Y. 等人：“转染色体小鼠中转移的人类 21 号染色体片段的种系传递”J.

Shinohara T., et al.: "Mice containing a human chrmosome 21 model behavioral impairment and cardiac anomalies of Down syndrome"Hum.Mol.Genet.. (in press).

Shinohara T. 等人：“含有人类 21 号染色体的小鼠模型行为障碍和唐氏综合症心脏异常”Hum.Mol.Genet..（出版中）。

Kazuki, Ye., et al.: "Germline transmission of a transferred human chromosome 21 fragment in transchromosomal mice"J.Hum.Genet.. 46. 600-603 (2001)

Kazuki, Ye., et al.：“转染色体小鼠中转移的人类 21 号染色体片段的种系传递”J.Hum.Genet.. 46. 600-603 (2001)