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Differential manifestation of ocular phenotypes in TALEN-mediated p19 arf knockout FVB/N and C57BL/6J mouse lines

 Jin-Sung Park  ;  Joo-Il Kim  ;  Hyun-Jin Lim  ;  Soo-Kyung Ryu  ;  Euna Kwon  ;  Kang-Min Han  ;  Ki-Taek Nam  ;  Han-Woong Lee  ;  Byeong-Cheol Kang 
 GENES & GENOMICS, Vol.42(9) : 1023-1033, 2020-09 
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Cataract ; Genetic background ; Mouse strain ; Phenotypic variability ; p19arf
Background: p19arf, primarily known as a tumor suppressor, has also been reported to play an essential role in normal development of mouse eyes. Consistently, lack of p19arf 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 p19arf KO associated phenotypes. Methods: We characterized the phenotypes of novel p19arf 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 p19arf-deficient mouse lines generated using homologous recombination. Results: Ninety-five percent of FVB/N-p19arf KO mice showed ocular opacity from week 4 after birth which worsened rapidly until week 6, while such abnormality was absent in C57BL/6J-p19arf KO mice up to the age of 26 weeks. Histopathological analysis revealed retrolental masses and dysplasia in the retinal layer in FVB/N-p19arf 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-p19arf KO mouse. Conclusion: Our findings demonstrated surprisingly variable manifestation of p19arf-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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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Nam, Ki Taek(남기택)
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