Department of Molecular Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, TX 78957, USA.
Exp Dermatol. 2012 Mar;21(3):217-20. doi: 10.1111/j.1600-0625.2011.01430.x.
Strains of mice vary in their susceptibility to ultra-violet (UV) radiation-induced skin tumors. Some strains of hairless mice (homozygous for the spontaneous Hr(hr) mutation) are particularly susceptible to these tumors. The skin tumors that develop in hairless mice resemble, both at the morphologic and molecular levels, UV-induced squamous cell carcinomas (SCC) and their precursors in human. The most commonly employed hairless mice belong to the SKH1 stock. However, these mice are outbred and their genetic background is not characterized, which makes them a poor model for genetic studies. We have developed a new inbred strain from outbred SKH1 mice that we named SKHIN/Sprd (now at generation F31). In order to characterize the genetic background of this new strain, we genotyped a cohort of mice at F30 with 92 microsatellites and 140 single nucleotide polymorphisms (SNP) evenly distributed throughout the mouse genome. We also exposed SKHIN/Sprd mice to chronic UV irradiation and showed that they are as susceptible to UV-induced skin carcinogenesis as outbred SKH1 mice. In addition, we proved that, albeit with low efficiency, inbred SKHIN/Sprd mice are suitable for transgenic production by classical pronuclear microinjection. This new inbred strain will be useful for the development of transgenic and congenic strains on a hairless inbred background as well as the establishment of syngeneic tumor cell lines. These new tools can potentially help elucidate a number of features of the cutaneous response to UV irradiation in humans, including the effect of genetic background and modifier genes.
不同品系的小鼠对紫外线(UV)辐射诱导的皮肤肿瘤的易感性存在差异。一些无毛小鼠(自发的 Hr(hr) 突变纯合)品系特别容易发生这些肿瘤。在无毛小鼠中发生的皮肤肿瘤在形态和分子水平上都类似于人类的 UV 诱导的鳞状细胞癌(SCC)及其前体。最常使用的无毛小鼠属于 SKH1 品系。然而,这些小鼠是杂交的,其遗传背景没有特征,这使得它们成为遗传研究的不良模型。我们从杂交的 SKH1 小鼠中开发了一种新的近交系,我们将其命名为 SKHIN/Sprd(现在处于 F31 代)。为了表征这个新品系的遗传背景,我们用 92 个微卫星和 140 个单核苷酸多态性(SNP)对 F30 代的一批小鼠进行了基因分型,这些 SNP 均匀分布在整个小鼠基因组中。我们还使 SKHIN/Sprd 小鼠暴露于慢性 UV 照射下,结果表明它们与杂交的 SKH1 小鼠一样容易发生 UV 诱导的皮肤癌变。此外,我们证明,尽管效率较低,近交系 SKHIN/Sprd 小鼠适合通过经典的原核显微注射进行转基因生产。这种新的近交系将有助于在无毛近交背景上开发转基因和同源系以及建立同源肿瘤细胞系。这些新工具可能有助于阐明人类对紫外线照射的皮肤反应的许多特征,包括遗传背景和修饰基因的影响。