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Kinga Bujakowska, Cecilia Maubaret, Christina F. Chakarova, Naoyuki Tanimoto, Susanne C. Beck, Edda Fahl, Marian M. Humphries, Paul F. Kenna, Evgeny Makarov, Olga Makarova, François Paquet-Durand, Per A. Ekström, Theo van Veen, Thierry Leveillard, Peter Humphries, Mathias W. Seeliger, Shomi S. Bhattacharya; Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP). Invest. Ophthalmol. Vis. Sci. 2009;50(12):5927-5933. doi: https://doi.org/10.1167/iovs.08-3275.
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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.
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.
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. Prpf31A216P/A216P and Prpf31 −/− genotypes were embryonic lethal.
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.
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