生物谷報(bào)道：傳統(tǒng)小鼠癌癥模型是通過將一種致癌基因轉(zhuǎn)移進(jìn)小鼠胚胎中做成的。轉(zhuǎn)移后實(shí)驗(yàn)鼠會患癌癥，但所患癌癥卻不會表現(xiàn)在人體中所發(fā)現(xiàn)的明顯的基因組不穩(wěn)定性,。人類癌癥一般與很多基因變異有關(guān),，其中有些是致癌的,，有些是正在形成中的疾病的構(gòu)成部分,，而有些則是偶然發(fā)生的。現(xiàn)在,，研究人員已經(jīng)培養(yǎng)出一個(gè)能夠模仿人類癌癥中基因組穩(wěn)定水平的新的小鼠模型,。該研究成果發(fā)表在最新一期的《Nature》雜志上。
研究人員是把能夠引起染色體不穩(wěn)定的遺傳要素用基因工程方法轉(zhuǎn)移進(jìn)易患淋巴癌的小鼠體內(nèi)而培養(yǎng)出這一小鼠模型的,，該模型在很多方面與人類疾病非常相似,，包括基因FBXW7 和 PTEN發(fā)生刪除和突變等。這種改進(jìn)的癌癥模型對于研究人類癌癥的發(fā)生機(jī)制具有重要意義,。
FIGURE 1. The TKO model.
a, Kaplan–Meier curve of thymic lymphoma-free survival for G3–G4 TKO mice with varying Trp53 dosage. b, Trp53 loss of heterozygosity assessed by PCR. N, normal; T, tumour. c, Representative FACS profile of a TKO tumour with CD4 and CD8 cell surface marker antibodies. d, Representative SKY images from metaphase spreads from G0 (upper panel) and G1–G4 (lower panel) lymphomas. e, Quantification of cytogenetic aberrations (recurrences) detected by SKY in G0 (blue) and G1–G4 (red) thymic lymphomas. Darker portion of column indicates proportion of non-reciprocal translocations; lighter portion indicates dicentric/robertsonian-like rearrangements. f, Recurrence plot of CNAs defined by array-CGH for 35 TKO lymphomas. The x axis shows the physical location of each chromosome. The percentage of tumours harbouring gains (dark red, log2 0.3), amplifications (bright red, log2 0.6), losses (green, log2 -0.3), and deletions (dark green, log2 -0.6) for each locus is depicted. Locations of physiologically relevant CNAs at Tcrb, Tcra/Tcrd and Tcrg (arrows), and Notch1 and Pten (asterisks) are indicated.
原文出處：
Nature Volume 447 Number 7147
Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers p966
Richard S. Maser, Bhudipa Choudhury, Peter J. Campbell, Bin Feng, Kwok-Kin Wong, Alexei Protopopov, Jennifer O'Neil, Alejandro Gutierrez, Elena Ivanova, Ilana Perna, Eric Lin, Vidya Mani, Shan Jiang, Kate McNamara, Sara Zaghlul, Sarah Edkins, Claire Stevens, Cameron Brennan, Eric S. Martin, Ruprecht Wiedemeyer, Omar Kabbarah, Cristina Nogueira, Gavin Histen, Jon Aster, Marc Mansour, Veronique Duke, Letizia Foroni, Adele K. Fielding, Anthony H. Goldstone, Jacob M. Rowe, Yaoqi A. Wang, A. Thomas Look, Michael R. Stratton, Lynda Chin, P. Andrew Futreal & Ronald A. DePinho
doi:10.1038/nature05886
Abstract | Full Text | PDF (767K) | Supplementary information
See also: Editor's summary
