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Yiwen Li, Byron L Lam, Ziqiang Guan, Zhengying Wang, Ning Wang, Yihui Chen, Rong Wen; Photoreceptor degeneration in the DHDDSK42E/K42E mouse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4371.
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© ARVO (1962-2015); The Authors (2016-present)
Transgenic DHDDSK42E/K42E mice were created to reconstruct the genotype of a human mutation recently identified in the DHDDS mice gene encoding dehydrodolichol diphosphate synthase (DHDDS). This mutation changes a highly conserved Lys42 to Glu and is responsible for 12% of autosomal recessive RP (arRP) cases in patients of Ashkenazi Jewish (AJ) origin. The present work characterizes the retinal degeneration in the DHDDSK42E/K42E mice.
Transgenic mice with DHDDSK42E genotype were created by the knock-in (KI) technology and bred into homozygosity. Animals were kept in <50 lux 12:12 cyclic light. Eyes were collected from 3 month old animals, embedded in an Epon/Araldite mixture, and sectioned at 1 µm thickness to display the entire retina along the vertical meridian. Retinal sections were examined by light microscopy.
The DHDDSK42E/K42E genotype was confirmed by PCR. A characteristic shortening of dolichol length distribution, similar to the shortening in patients, was found in plasma dolichols by liquid chromatography-mass spectrometry. In the 3 months DHDDSK42E/K42E mice, the outer segments (OS) of rod photoreceptors reduced to about half of the length seen in the age matched wild-type (wt) animals. In addition, the outer nuclear layer (ONL) thickness decreased to two-thirds compared to that of the wt controls.
The DHDDSK42E/K42E mice recapitulate the phenotype of retinal degeneration in patients and are a viable model of arRP caused by the K42E DHDDS mutation.
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