Differential manifestation of ocular phenotypes in TALEN-mediatedp19(arf)knockout FVB/N and C57BL/6J mouse lines

초록

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 ofp19(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 ofp19(arf)KO associated phenotypes. Methods We characterized the phenotypes of novelp19(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 otherp19(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 ofp19(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.

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