TMEM216 Deletion Causes Mislocalization of Cone Opsin and Rhodopsin and Photoreceptor Degeneration in Zebrafish

Investigative Ophthalmology & Visual Science
Yu LiuHuaiyu Hu

Abstract

Mutations in TMEM216, a ciliary transition zone tetraspan transmembrane protein, are linked to Joubert syndrome and Meckel syndrome. Photoreceptor degeneration is a prominent phenotype in Joubert syndrome. How TMEM216 contributes to photoreceptor health is poorly understood. We have generated tmem216 knockout zebrafish by CRISPR genome editing. The impact of TMEM216 deletion on photoreceptors was evaluated by immunofluorescence staining and electron microscopy. Homozygous tmem216 knockout zebrafish died before 21 days after fertilization. Their retina exhibited reduced immunoreactivity to rod photoreceptor outer segment marker 4D2 and cone photoreceptor outer segment marker G protein subunit α transducin 2 (GNAT2). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) revealed an increase in TUNEL-positive nuclei in the knockout retina, indicating photoreceptor degeneration. The tmem216 mutation resulted in shortened photoreceptor ciliary axoneme, as revealed by acetylated α-tubulin immunostaining. Photoreceptors in knockout zebrafish exhibited mislocalization of outer segment proteins such as rhodopsin, GNAT2, and red opsin to the inner segment and cell bodies. Additionally, electron microscopy revealed that the...Continue Reading

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Methods Mentioned

BETA
electrophoresis
in vitro transcription
Knockout
PCR
genotyping
transmission electron microcopy

Software Mentioned

ImageJ

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