title: Study of gene-targeted mouse models of splicing factor gene Prpf31 implicated in human autosomal dominant retinitis pigmentosa (RP).
abstract: OBJECTIVE
  Pre-mRNA processing factor 31 (PRPF31) is a ubiquitous protein needed for the assembly of the pre-mRNA splicing machinery. It has been shown that mutations in this gene cause autosomal dominant retinitis pigmentosa 11 (RP11), which is characterized by rod-cell degeneration. Interestingly, mutations in this ubiquitously expressed gene do not lead to phenotypes other than retinal malfunction. Furthermore, the dominant inheritance pattern has shown incomplete penetrance, which poses interesting questions about the disease mechanism of RP11.
  
  
  METHODS
  To characterize PRPF31 function in the rod cells, two animal models have been generated. One was a heterozygous knock-in mouse (Prpf31(A216P/+)) carrying a point mutation p.A216P, which has previously been identified in RP11 patients. The second was a heterozygous knockout mouse (Prpf31(+/-)). Retinal degeneration in RP11 mouse models was monitored by electroretinography and histology.
  
  
  RESULTS
  Generation of the mouse models is presented, as are results of ERGs and retinal morphology. No degenerative phenotype on fundus examination was found in Prpf31(A216P/+) and Prpf31(+/-) mice. Prpf31(A216P/A216P) and Prpf31(-/-) genotypes were embryonic lethal.
  
  
  CONCLUSIONS
  The results imply that Prpf31 is necessary for survival, and there is no compensation mechanism in mouse for the lack of this splicing factor. The authors suggest that p.A216P mutation in Prpf31 does not exert a dominant negative effect and that one Prpf31 wild-type allele is sufficient for maintenance of the healthy retina in mice.
authors: Institute of Ophthalmology, University College London, London, United Kingdom.
authors: Kinga
authors: K
authors: Bujakowska
authors: Cecilia
authors: C
authors: Maubaret
authors: Christina F
authors: CF
authors: Chakarova
authors: Naoyuki
authors: N
authors: Tanimoto
authors: Susanne C
authors: SC
authors: Beck
authors: Edda
authors: E
authors: Fahl
authors: Marian M
authors: MM
authors: Humphries
authors: Paul F
authors: PF
authors: Kenna
authors: Evgeny
authors: E
authors: Makarov
authors: Olga
authors: O
authors: Makarova
authors: François
authors: F
authors: Paquet-Durand
authors: Per A
authors: PA
authors: Ekström
authors: Theo
authors: T
authors: van Veen
authors: Thierry
authors: T
authors: Leveillard
authors: Peter
authors: P
authors: Humphries
authors: Mathias W
authors: MW
authors: Seeliger
authors: Shomi S
authors: SS
authors: Bhattacharya
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D055879:Gene Knock-In Techniques; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009887:Ophthalmoscopy; D017354:Point Mutation; D012160:Retina / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology
chemical_list: D005136:Eye Proteins; C454222:PRPF31 protein, human