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Mouse Models of Achromatopsia in Addressing Temporal “Point of No Return” in Gene-Therapy by Nan-Kai Wang; Pei-Kang Liu; Yang Kong; Sarah R. Levi; Wan-Chun Huang; Chun-Wei Hsu; Hung-Hsi Wang; Nelson Chen; Yun-Ju Tseng; Peter M. J. Quinn; Ming-Hong Tai; Chyuan-Sheng Lin; Stephen H. Tsang is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Mouse Models of Achromatopsia in Addressing Temporal “Point of No Return” in Gene-Therapy about?

Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery remains unknown. Here, we attempted two rounds of gene augmentation to generate recoverable mouse models of achromatopsia including a __Cnga3__ model with a knock-in stop cassette in intron 5 using __Easi__-CRISPR (__E__fficient __a__dditions with __s__sDNA __i__nserts-CRISPR) and targeted embryonic stem (ES) cells. This model demonstrated that only 20% of CNGA3 levels in homozygotes derived from target ES cells remained, as compared to normal CNGA3 levels. Despite the low percentage of remaining protein, the knock-in mouse model continued to generate normal cone phototransduction. Our results showed that a small amount of normal CNGA3 protein is sufficient to form “functional” CNG channels and achieve physiological demand for proper cone phototransduction. Thus, it can be concluded that mutating the __Cnga3__ locus to disrupt the functional tetrameric CNG channels may ultimately require more potent STOP cassettes to g

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Author

Nan-Kai Wang; Pei-Kang Liu; Yang Kong; Sarah R. Levi; Wan-Chun Huang; Chun-Wei Hsu; Hung-Hsi Wang; Nelson Chen; Yun-Ju Tseng; Peter M. J. Quinn; Ming-Hong Tai; Chyuan-Sheng Lin; Stephen H. Tsang

Publisher

MDPI AG

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)