May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Prpf31 Knock-In Mouse as a Model of Retinitis Pigmentosa 11
Author Affiliations & Notes
  • K. M. Bujakowska
    Molecular Genetics, Institute of Ophthalmology/UCL, London, United Kingdom
    Institut de la Vision, Paris, France
  • C. Maubaret
    Molecular Genetics, Institute of Ophthalmology/UCL, London, United Kingdom
  • N. Tanimoto
    Centre for Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany
  • S. C. Beck
    Centre for Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany
  • E. Fahl
    Centre for Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany
  • M. M. Humphries
    Ocular Genetics Unit, Trinity College, Dublin, Ireland
  • P. Kenna
    Ocular Genetics Unit, Trinity College, Dublin, Ireland
  • P. Humphries
    Ocular Genetics Unit, Trinity College, Dublin, Ireland
  • M. W. Seeliger
    Centre for Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany
  • S. S. Bhattacharya
    Molecular Genetics, Institute of Ophthalmology/UCL, London, United Kingdom
    Institut de la Vision, Paris, France
  • Footnotes
    Commercial Relationships  K.M. Bujakowska, None; C. Maubaret, None; N. Tanimoto, None; S.C. Beck, None; E. Fahl, None; M.M. Humphries, None; P. Kenna, None; P. Humphries, None; M.W. Seeliger, None; S.S. Bhattacharya, None.
  • Footnotes
    Support  EU Marie Curie -TN 2003-504003
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2196. doi:
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      K. M. Bujakowska, C. Maubaret, N. Tanimoto, S. C. Beck, E. Fahl, M. M. Humphries, P. Kenna, P. Humphries, M. W. Seeliger, S. S. Bhattacharya; Prpf31 Knock-In Mouse as a Model of Retinitis Pigmentosa 11. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2196.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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 characterised by rod-cell degeneration. Interestingly, mutations in this ubiquitously expressed gene do not lead to other phenotypes than retinal malfunction. Furthermore, the dominant inheritance pattern has shown incomplete penetrance which poses interesting questions about the disease mechanism of RP11.

Methods: : In order to characterise the specificity of PRPF31 function in the rod cells, an animal model has been generated. This is a knock-in (KI) mouse carrying a point mutation A216P, which has been previously identified in RP11 patients. Retinal degeneration in Prpf31A216P/+ mice was monitored by electroretinography (ERG) and histology. The level of Prpf31 expression in Prpf31A216P/+ mice and different mouse strains was investigated with real time quantitative PCR.

Results: : Generation of the mouse model will be presented as well as results of retinal function and morphology. Up to 18 months of age, no degenerative phenotype was found in Prpf31A216P/+ mice. A216P mutation of PRPF31 in homozygous state was found to be lethal and there were no Prpf31A216P/A216P embryos found at E10. These results imply that A216P mutation affects Prpf31 protein function and that there is no compensation effect from other proteins. Quantitative PCR experiments have demonstrated a differential expression of the Prpf31 gene in various mouse strains, where Prpf31A216P/+ mice expressed 24% more than the lowest expressing strain C57BL/6J.

Conclusions: : This work suggests that similarly to partial penetrance in RP11 patients, lack of retinal phenotype in Prpf31A216P/+ mice might be caused by a highly expressing Prpf31 allele.

Keywords: retinitis 
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