Genetic Factors on Mouse Chromosome 18 Affecting Susceptibility to Testicular Germ Cell Tumors and Permissiveness to Embryonic Stem Cell Derivation
Genetic Factors on Mouse Chromosome 18 Affecting Susceptibility to Testicular Germ Cell Tumors and Permissiveness to Embryonic Stem Cell Derivation
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DOI：
10.1158/0008-5472.can-09-3342
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发表时间：
2009-12-01
期刊：
影响因子：
11.2
通讯作者：
Nadeau, Joseph H.
中科院分区：
文献类型：
--
作者：
Anderson, Philip D.;Nelson, Vicki R.;Nadeau, Joseph H.
尽管有很强的遗传性，但对人类或小鼠睾丸生殖细胞肿瘤（TGCT）易感性的遗传控制知之甚少。虽然小鼠模型的自发TGCT已被广泛研究，传统的连锁分析未能找到的因素，控制畸胎瘤的易感129家庭的近交系。作为一种替代方法，我们使用染色体置换菌株（CSS）来识别携带易感基因的单个染色体，并使用一组来自选定CSS的同源菌株来确定置换染色体上易感性变体的数量和位置。我们发现，129-Chr 18（MOLF）男性对自发TGCT具有抗性，并且至少有四种遗传变异控制了具有这种取代染色体的男性的易感性。此外，来自该品系的早期胚胎细胞不能像来自亲本129/Sv品系的那些细胞那样有效地建立胚胎干细胞系。这是第一次，控制TGCT易感性和胚胎干细胞生物学基本方面的129个衍生遗传变异已被定位在遗传背景下，其中基因可以被识别和功能特征。[Cancer Res 2009; 69（23）：9112 - 7]
Despite strong heritability, little is known about the genetic control of susceptibility to testicular germ cell tumors (TGCT) in humans or mice. Although the mouse model of spontaneous TGCTs has been extensively studied, conventional linkage analysis has failed to locate the factors that control teratocarcinogenesis in the susceptible 129 family of inbred strains. As an alternative approach, we used both chromosome substitution strains (CSS) to identify individual chromosomes that harbor susceptibility genes and a panel of congenic strains derived from a selected CSS to determine the number and location of susceptibility variants on the substituted chromosome. We showed that 129-Chr 18(MOLF) males are resistant to spontaneous TGCTs and that at least four genetic variants control susceptibility in males with this substituted chromosome. In addition, early embryonic cells from this strain fail to establish embryonic stem cell lines as efficiently as those from the parental 129/Sv strain. For the first time, 129-derived genetic variants that control TGCT susceptibility and fundamental aspects of embryonic stem cell biology have been localized in a genetic context in which the genes can be identified and functionally characterized. [Cancer Res 2009;69(23):9112-7]