title: A transgenic mouse model for gene therapy of rhodopsin-linked Retinitis Pigmentosa.
abstract: Mutational heterogeneity in genes causative of dominantly inherited disorders represents a significant barrier for development of therapies directed towards correction of the primary genetic defect. To circumvent the mutational heterogeneity present in rhodopsin- (RHO-) linked autosomal dominant Retinitis Pigmentosa (adRP), a strategy involving suppression and replacement of RHO has been adopted. RNA interference- (RNAi-) mediated suppression of RHO has been explored as has the generation of an RNAi-resistant replacement gene using the degeneracy of the genetic code. Additionally, the functional equivalence of codon-modified replacement genes has been demonstrated in a transgenic animal (RHO-M). Suppression and replacement, while exemplified by adRP, may also be relevant to many other dominantly inherited diseases with the hallmark of mutational heterogeneity.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. oreillym@tcd.ie
authors.forename: Mary
authors.initials: M
authors.lastname: O'Reilly
authors.forename: Sophia
authors.initials: S
authors.lastname: Millington-Ward
authors.forename: Arpad
authors.initials: A
authors.lastname: Palfi
authors.forename: Naomi
authors.initials: N
authors.lastname: Chadderton
authors.forename: Thérèse
authors.initials: T
authors.lastname: Cronin
authors.forename: Niamh
authors.initials: N
authors.lastname: McNally
authors.forename: Marian M
authors.initials: MM
authors.lastname: Humphries
authors.forename: Peter
authors.initials: P
authors.lastname: Humphries
authors.forename: Paul F
authors.initials: PF
authors.lastname: Kenna
authors.forename: G Jane
authors.initials: GJ
authors.lastname: Farrar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004596:Electroretinography; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012243:Rhodopsin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012243:Rhodopsin