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.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, 506 McKnight Building, 1638 NW 10th Ave, 33136, Miami, FL, USA, rwen@med.miami.edu.
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
authors.forename: Julia E
authors.initials: JE
authors.lastname: Dallman
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Züchner
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Peričak-Vance
authors.forename: Byron L
authors.initials: BL
authors.lastname: Lam
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D007438:Introns / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins; D019883:Alkyl and Aryl Transferases; C051389:dehydrodolichyl diphosphate synthetase