PMID- 32687549
OWN - NLM
STAT- MEDLINE
DCOM- 20210101
LR  - 20231130
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 61
IP  - 8
DP  - 2020 Jul 1
TI  - TMEM216 Deletion Causes Mislocalization of Cone Opsin and Rhodopsin and 
      Photoreceptor Degeneration in Zebrafish.
PG  - 24
LID - 10.1167/iovs.61.8.24 [doi]
LID - 24
AB  - PURPOSE: 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. METHODS: 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. RESULTS: 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 alpha 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 alpha-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 
      mutant photoreceptors elaborated outer segment with abnormal disc morphology such 
      as shortened discs and vesicles/vacuoles within the outer segment. CONCLUSION: 
      Our results indicate that TMEM216 is essential for normal genesis of outer 
      segment disc structures, transport of outer segment materials, and survival of 
      photoreceptors in zebrafish. These tmem216 knockout zebrafish will be useful in 
      studying how transition zone proteins regulate photoreceptor outer segment 
      formation and maintenance.
FAU - Liu, Yu
AU  - Liu Y
AD  - .
FAU - Cao, Shuqin
AU  - Cao S
AD  - .
FAU - Yu, Miao
AU  - Yu M
AD  - .
FAU - Hu, Huaiyu
AU  - Hu H
AD  - .
LA  - eng
GR  - R01 EY028555/EY/NEI NIH HHS/United States
GR  - R01 HD083680/HD/NICHD NIH HHS/United States
GR  - R21 EY031002/EY/NEI NIH HHS/United States
GR  - R21 EY031119/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cone Opsins)
RN  - 0 (Membrane Proteins)
RN  - 0 (TMEM216 protein, human)
RN  - 0 (Zebrafish Proteins)
RN  - 9009-81-8 (Rhodopsin)
SB  - IM
MH  - Animals
MH  - Cone Opsins/*metabolism
MH  - Gene Knockout Techniques
MH  - Humans
MH  - *Membrane Proteins/genetics/metabolism
MH  - Mutation
MH  - Photoreceptor Cells/*physiology
MH  - Retinal Degeneration/genetics
MH  - Rhodopsin/*metabolism
MH  - Zebrafish
MH  - Zebrafish Proteins/*genetics
PMC - PMC7425700
COIS- Disclosure: Y. Liu, None; S. Cao, None; M. Yu, None; H. Hu, None
EDAT- 2020/07/21 06:00
MHDA- 2021/01/02 06:00
PMCR- 2020/07/20
CRDT- 2020/07/21 06:00
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2021/01/02 06:00 [medline]
PHST- 2020/07/20 00:00 [pmc-release]
AID - 2770336 [pii]
AID - IOVS-19-29036 [pii]
AID - 10.1167/iovs.61.8.24 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2020 Jul 1;61(8):24. doi: 10.1167/iovs.61.8.24.