Mouse Model for Retinoblastoma Research

Cancer researchers working with mice have learned that the tumor suppressor Rb protein, which when lacking can trigger retinoblastoma in young children, limits the proliferation of immature retinal cells in developing embryos and prompts specific cells to mature into light-sensitive retinal rods.

The role of Rb in the developing mouse retina had not been studied previously, as Rb-deficient embryos die before the retinas are fully formed. In the current work, investigators at St. Jude Children's Research Hospital (Memphis, TN, USA) devised several new approaches for studying Rb. These techniques include methods for knocking out Rb expression in cultured mouse retinal cells, as well as methods for knocking out Rb in single retinal progenitor cells so the effect of this mutation could be studied in both embryos and newborn mice.

A viral vector was used to insert the gene for E1A-a protein that inactivates Rb in newborn mice, whose retinas continue to develop after birth. The retinas in these newborn mice grew abnormally large and failed to develop rods. The investigators reported in the February 29, 2004, online edition of Nature Genetics that Rb was required for both proper regulation of retinal cell proliferation and for initiation of rod formation.

"Our work has also included efforts to develop a mouse model that has the same genetic mutations as those found in humans with retinoblastoma yet permits the mouse to develop and be born,” explained senior author Dr. Michael A. Dyer, assistant professor of neurobiology at St. Jude Children's Research Hospital. "This will further enhance our understanding of this devastating cancer and allow us to test new treatments that will spare children with this cancer from losing one or both eyes.”




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