Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP)

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Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP). / Bujakowska, Kinga; Maubaret, Cecilia; Chakarova, Christina F.; Tanimoto, Naoyuki; Beck, Susanne C.; Fahl, Edda; Humphries, Marian M.; Kenna, Paul F.; Makarov, Evgeny; Makarova, Olga; Paquet-Durand, Francois; Ekström, Per; van Veen, Theo; Leveillard, Thierry; Humphries, Peter; Seeliger, Mathias W.; Bhattacharya, Shomi S.

I: Investigative Ophthalmology & Visual Science, Vol. 50, Nr. 12, 2009, s. 5927-5933.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Bujakowska, K, Maubaret, C, Chakarova, CF, Tanimoto, N, Beck, SC, Fahl, E, Humphries, MM, Kenna, PF, Makarov, E, Makarova, O, Paquet-Durand, F, Ekström, P, van Veen, T, Leveillard, T, Humphries, P, Seeliger, MW & Bhattacharya, SS 2009, 'Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP)', Investigative Ophthalmology & Visual Science, vol. 50, nr. 12, s. 5927-5933. https://doi.org/10.1167/iovs.08-3275

APA

CBE

Bujakowska K, Maubaret C, Chakarova CF, Tanimoto N, Beck SC, Fahl E, Humphries MM, Kenna PF, Makarov E, Makarova O, Paquet-Durand F, Ekström P, van Veen T, Leveillard T, Humphries P, Seeliger MW, Bhattacharya SS. 2009. Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP). Investigative Ophthalmology & Visual Science. 50(12):5927-5933. https://doi.org/10.1167/iovs.08-3275

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Author

Bujakowska, Kinga ; Maubaret, Cecilia ; Chakarova, Christina F. ; Tanimoto, Naoyuki ; Beck, Susanne C. ; Fahl, Edda ; Humphries, Marian M. ; Kenna, Paul F. ; Makarov, Evgeny ; Makarova, Olga ; Paquet-Durand, Francois ; Ekström, Per ; van Veen, Theo ; Leveillard, Thierry ; Humphries, Peter ; Seeliger, Mathias W. ; Bhattacharya, Shomi S. / Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP). I: Investigative Ophthalmology & Visual Science. 2009 ; Vol. 50, Nr. 12. s. 5927-5933.

RIS

TY - JOUR

T1 - Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP)

AU - Bujakowska, Kinga

AU - Maubaret, Cecilia

AU - Chakarova, Christina F.

AU - Tanimoto, Naoyuki

AU - Beck, Susanne C.

AU - Fahl, Edda

AU - Humphries, Marian M.

AU - Kenna, Paul F.

AU - Makarov, Evgeny

AU - Makarova, Olga

AU - Paquet-Durand, Francois

AU - Ekström, Per

AU - van Veen, Theo

AU - Leveillard, Thierry

AU - Humphries, Peter

AU - Seeliger, Mathias W.

AU - Bhattacharya, Shomi S.

PY - 2009

Y1 - 2009

N2 - 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 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.

AB - 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 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.

U2 - 10.1167/iovs.08-3275

DO - 10.1167/iovs.08-3275

M3 - Article

VL - 50

SP - 5927

EP - 5933

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 1552-5783

IS - 12

ER -