Knock-down DHDDS expression induces photoreceptor degeneration in zebrafish.

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Abstract

A mutation in the dehydrodolichol diphosphate synthase (DHDDS) was recently identified as the cause of a subtype of recessive retinitis pigmentosa (RP). Molecular modeling indicates that this mutation could result in low enzymatic efficiency of DHDDS. To investigate the possible link between insufficient DHDDS activity and photoreceptor degeneration, the expression of DHDDS was knocked down by morpholino oligonucleotides (MO) injected into zebrafish one cell embryos. The general appearance and behavior of 4-day-old MO-injected fish were normal, but they failed to respond to light-off, suggesting loss of visual function. Morphological analysis showed that photoreceptor outer segments in retinas of MO-injected fish are very short and in many cases completely missing. Peanut agglutinin (PNA) staining confirmed the absence of cone outer segments. These results demonstrate that suppression of DHDDS expression in zebrafish leads to the loss of photoreceptor outer segments and visual function. These results support the hypothesis that insufficient DHDDS function leads to retinal degeneration.

Original languageEnglish
Pages (from-to)543-550
Number of pages8
JournalAdvances in Experimental Medicine and Biology
Volume801
DOIs
StatePublished - Jan 1 2014

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Diphosphates
Zebrafish
Morpholinos
Fish
Fishes
Peanut Agglutinin
Retinal Degeneration
Mutation
Molecular modeling
Retinitis Pigmentosa
Retina
dehydrodolichol
Cones
Embryonic Structures
Staining and Labeling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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title = "Knock-down DHDDS expression induces photoreceptor degeneration in zebrafish.",
abstract = "A mutation in the dehydrodolichol diphosphate synthase (DHDDS) was recently identified as the cause of a subtype of recessive retinitis pigmentosa (RP). Molecular modeling indicates that this mutation could result in low enzymatic efficiency of DHDDS. To investigate the possible link between insufficient DHDDS activity and photoreceptor degeneration, the expression of DHDDS was knocked down by morpholino oligonucleotides (MO) injected into zebrafish one cell embryos. The general appearance and behavior of 4-day-old MO-injected fish were normal, but they failed to respond to light-off, suggesting loss of visual function. Morphological analysis showed that photoreceptor outer segments in retinas of MO-injected fish are very short and in many cases completely missing. Peanut agglutinin (PNA) staining confirmed the absence of cone outer segments. These results demonstrate that suppression of DHDDS expression in zebrafish leads to the loss of photoreceptor outer segments and visual function. These results support the hypothesis that insufficient DHDDS function leads to retinal degeneration.",
author = "Rong Wen and Julia Dallman and Yiwen Li and Zuchner, {Stephan L} and Vance, {Jeffery M} and Pericak-Vance, {Margaret A} and Lam, {Byron L}",
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T1 - Knock-down DHDDS expression induces photoreceptor degeneration in zebrafish.

AU - Wen, Rong

AU - Dallman, Julia

AU - Li, Yiwen

AU - Zuchner, Stephan L

AU - Vance, Jeffery M

AU - Pericak-Vance, Margaret A

AU - Lam, Byron L

PY - 2014/1/1

Y1 - 2014/1/1

N2 - A mutation in the dehydrodolichol diphosphate synthase (DHDDS) was recently identified as the cause of a subtype of recessive retinitis pigmentosa (RP). Molecular modeling indicates that this mutation could result in low enzymatic efficiency of DHDDS. To investigate the possible link between insufficient DHDDS activity and photoreceptor degeneration, the expression of DHDDS was knocked down by morpholino oligonucleotides (MO) injected into zebrafish one cell embryos. The general appearance and behavior of 4-day-old MO-injected fish were normal, but they failed to respond to light-off, suggesting loss of visual function. Morphological analysis showed that photoreceptor outer segments in retinas of MO-injected fish are very short and in many cases completely missing. Peanut agglutinin (PNA) staining confirmed the absence of cone outer segments. These results demonstrate that suppression of DHDDS expression in zebrafish leads to the loss of photoreceptor outer segments and visual function. These results support the hypothesis that insufficient DHDDS function leads to retinal degeneration.

AB - A mutation in the dehydrodolichol diphosphate synthase (DHDDS) was recently identified as the cause of a subtype of recessive retinitis pigmentosa (RP). Molecular modeling indicates that this mutation could result in low enzymatic efficiency of DHDDS. To investigate the possible link between insufficient DHDDS activity and photoreceptor degeneration, the expression of DHDDS was knocked down by morpholino oligonucleotides (MO) injected into zebrafish one cell embryos. The general appearance and behavior of 4-day-old MO-injected fish were normal, but they failed to respond to light-off, suggesting loss of visual function. Morphological analysis showed that photoreceptor outer segments in retinas of MO-injected fish are very short and in many cases completely missing. Peanut agglutinin (PNA) staining confirmed the absence of cone outer segments. These results demonstrate that suppression of DHDDS expression in zebrafish leads to the loss of photoreceptor outer segments and visual function. These results support the hypothesis that insufficient DHDDS function leads to retinal degeneration.

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