Background

p19^arf, primarily known as a tumor suppressor, has also been reported to play an essential role in normal development of mouse eyes. Consistently, lack of p19^arf has been associated with ocular defects, but the mixed background of the knockout (KO) mouse strain used raised a concern on the accuracy of the phenotypes observed in association with the targeted gene due to genetic heterogeneity.

Object

We carried out a study to investigate into the effect of genetic background on the manifestation of p19^arf KO associated phenotypes.

Methods

We characterized the phenotypes of novel p19^arf KO mouse lines generated in FVB/N and C57BL/6J using a transcription activator-like effector nuclease (TALEN) system in comparison to the reported phenotypes of three other p19^arf-deficient mouse lines generated using homologous recombination.

Results

Ninety-five percent of FVB/N-p19^arf KO mice showed ocular opacity from week 4 after birth which worsened rapidly until week 6, while such abnormality was absent in C57BL/6J-p19^arf KO mice up to the age of 26 weeks. Histopathological analysis revealed retrolental masses and dysplasia in the retinal layer in FVB/N-p19^arf KO mice from week 4. Besides these, both strains developed normally from birth to week 26 without increased tumorigenesis except for a subcutaneous tumor found in a C57BL/6J-p19^arf KO mouse.

Conclusion

Our findings demonstrated surprisingly variable manifestation of p19^arf-linked phenotypes between FVB/N and C57BL/6J mice, and furthermore between our mouse lines and the established lines, indicating a critical impact of genetic background on functional study of genes using gene targeting strategies in mice.

中文翻译：

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在TALEN介导的p19arf基因敲除的FVB / N和C57BL / 6J小鼠品系中眼表型的差异表现。

背景

p19 ^arf主要被称为肿瘤抑制因子，据报道在小鼠眼睛的正常发育中也起着至关重要的作用。一致地，缺乏p19 ^arf与眼缺陷有关，但是由于遗传异质性，所使用的基因敲除（KO）小鼠品系的混合背景引起了与目标基因相关的表型准确性的关注。

目的

我们进行了一项研究，以调查遗传背景对p19 ^arf KO相关表型的表现的影响。

方法

我们表征新颖的表型P19 ^ARF在FVB / N和C57BL / 6J产生KO小鼠品系使用类转录活化因子核酸酶（TALEN）系统相对于其他三个报告表型的p19 ^ARF使用同源产生的缺陷型小鼠系重组。

结果

FVB的百分之九十五/ N- P19 ^ARF基因敲除小鼠表现出4周眼混浊生可迅速恶化，直到第6周后，尽管这样的异常在C57BL / 6J-缺席P19 ^ARF基因敲除小鼠26周的年龄。组织病理学分析显示，从第4周开始，FVB / N- p19 ^arf KO小鼠的视网膜层存在视网膜后增生和异型增生。此外，这两种菌株从出生到第26周均正常发育，除了C57BL / 6J中发现的皮下肿瘤外，其肿瘤形成没有增加- P19 ^ARF KO鼠标。

结论

我们的发现证明FVB / N和C57BL / 6J小鼠之间，以及我们的小鼠系与既定系之间p19 ^arf连锁表型的表现出乎意料的变化，这表明遗传背景对基因功能研究的关键性影响在于遗传背景。老鼠。