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Michael O'Hare, Shadmand Mehdi, Timothy William Corson; Kif14 overexpression accelerates tumor development in the TAg-RB transgenic model of retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):74.
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The mitotic kinesin KIF14 is a molecular motor that plays a pivotal role in the final stages of cytokinesis. In most cases of retinoblastoma the KIF14 locus at 1q32.1 is gained as an important event after mutation of the RB1 gene. Moreover, KIF14 is overexpressed in retinoblastoma, strongly suggesting its role as an oncogene. Despite this, KIF14’s effects on retinoblastoma in vivo have not previously been analyzed. We aimed to determine Kif14’s role in promoting retinal tumor formation using a novel Kif14 overexpressing, TAg-RB retinoblastoma mouse model. Understanding the effects of Kif14 overexpression in vivo will allow for a greater understanding of the biology of post RB1 loss events and how they contribute to retinoblastoma progression.
By crossing transgenic mice constitutively overexpressing Kif14 into the SV40 T-antigen expressing model of retinoblastoma (TAg-RB) we generated Kif14; TAg-RB double transgenic mice. The Micron III rodent imaging system was used to obtain fundus photographs as well as optical coherence tomography (OCT) images. Double transgenics and TAg-RB littermates were imaged in both eyes over a time-course to document tumor development.
Compared to the TAg-RB single transgenic mice, the Kif14; TAg-RB double transgenic mice showed greatly accelerated formation of tumor-like clusters of hyper-reflective cells in the inner nuclear layer of the retina from as early as 3-4 weeks of age, as visualized by OCT. Pale intraretinal tumors were first visible by funduscopy in the periphery of the retina by week 6 in the Kif14; TAg-RB mice compared to week 8 in the TAg-RB mice.
The over-expression of the Kif14 oncogene in the TAg-RB model of retinoblastoma leads to accelerated onset of tumor formation, providing strong evidence that Kif14 promotes retinoblastoma formation in vivo. Further investigation will include quantitative immunohistochemical analysis of these mice to complement the OCT findings and further validate the importance of Kif14 for the genesis of retinoblastoma.
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