PMID- 26009893
OWN - NLM
STAT- MEDLINE
DCOM- 20160418
LR  - 20220330
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 5
DP  - 2015
TI  - Genotypic and phenotypic characterization of P23H line 1 rat model.
PG  - e0127319
LID - 10.1371/journal.pone.0127319 [doi]
LID - e0127319
AB  - Rod-cone dystrophy, also known as retinitis pigmentosa (RP), is the most common 
      inherited degenerative photoreceptor disease, for which no therapy is currently 
      available. The P23H rat is one of the most commonly used autosomal dominant RP 
      models. It has been created by incorporation of a mutated mouse rhodopsin (Rho) 
      transgene in the wild-type (WT) Sprague Dawley rat. Detailed genetic 
      characterization of this transgenic animal has however never been fully reported. 
      Here we filled this knowledge gap on P23H Line 1 rat (P23H-1) and provide 
      additional phenotypic information applying non-invasive and state-of-the-art in 
      vivo techniques that are relevant for preclinical therapeutic evaluations. 
      Transgene sequence was analyzed by Sanger sequencing. Using quantitative PCR, 
      transgene copy number was calculated and its expression measured in retinal 
      tissue. Full field electroretinography (ERG) and spectral domain optical 
      coherence tomography (SD-OCT) were performed at 1-, 2-, 3- and 6-months of age. 
      Sanger sequencing revealed that P23H-1 rat carries the mutated mouse genomic Rho 
      sequence from the promoter to the 3' UTR. Transgene copy numbers were estimated 
      at 9 and 18 copies in the hemizygous and homozygous rats respectively. In 
      1-month-old hemizygous P23H-1 rats, transgene expression represented 43% of all 
      Rho expressed alleles. ERG showed a progressive rod-cone dysfunction peaking at 6 
      months-of-age. SD-OCT confirmed a progressive thinning of the photoreceptor cell 
      layer leading to the disappearance of the outer retina by 6 months with 
      additional morphological changes in the inner retinal cell layers in hemizygous 
      P23H-1 rats. These results provide precise genotypic information of the P23H-1 
      rat with additional phenotypic characterization that will serve basis for 
      therapeutic interventions, especially for those aiming at gene editing.
FAU - Orhan, Elise
AU  - Orhan E
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Dalkara, Deniz
AU  - Dalkara D
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Neuille, Marion
AU  - Neuille M
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Lechauve, Christophe
AU  - Lechauve C
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Michiels, Christelle
AU  - Michiels C
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Picaud, Serge
AU  - Picaud S
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Leveillard, Thierry
AU  - Leveillard T
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Sahel, Jose-Alain
AU  - Sahel JA
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France; Centre 
      Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, 
      INSERM-DHOS CIC 1423, Paris, France; Institute of Ophthalmology, University 
      College of London, London, United Kingdom; Fondation Ophtalmologique Adolphe de 
      Rothschild, Paris, France; Academie des Sciences, Institut de France, Paris, 
      France.
FAU - Naash, Muna I
AU  - Naash MI
AD  - Department of Cell Biology, University of Oklahoma Health Sciences Center, 
      Oklahoma City, Oklahoma, United States of America.
FAU - Lavail, Matthew M
AU  - Lavail MM
AD  - Department of Ophthalmology, University of California San Francisco, San 
      Francisco, California, United States of America; Department of Anatomy, 
      University of California San Francisco, San Francisco, California United States 
      of America.
FAU - Zeitz, Christina
AU  - Zeitz C
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Audo, Isabelle
AU  - Audo I
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France; Centre 
      Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, 
      INSERM-DHOS CIC 1423, Paris, France; Institute of Ophthalmology, University 
      College of London, London, United Kingdom.
LA  - eng
GR  - R01 EY010609/EY/NEI NIH HHS/United States
GR  - EY10609/EY/NEI NIH HHS/United States
GR  - F32 EY006842/EY/NEI NIH HHS/United States
GR  - R01 EY006842/EY/NEI NIH HHS/United States
GR  - R01 EY001919/EY/NEI NIH HHS/United States
GR  - R56 EY010609/EY/NEI NIH HHS/United States
GR  - EY001919/EY/NEI NIH HHS/United States
GR  - EY006842/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150526
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 9009-81-8 (Rhodopsin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Color Vision
MH  - Disease Models, Animal
MH  - Electroretinography
MH  - Gene Dosage
MH  - Hemizygote
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - Phenotype
MH  - Rats, Sprague-Dawley
MH  - Rats, Transgenic
MH  - Retina/pathology
MH  - Retinitis Pigmentosa/*genetics
MH  - Rhodopsin/chemistry/*genetics
MH  - Sequence Analysis, DNA
MH  - Tomography, Optical Coherence
MH  - Transgenes
PMC - PMC4444340
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/05/27 06:00
MHDA- 2016/04/19 06:00
PMCR- 2015/05/26
CRDT- 2015/05/27 06:00
PHST- 2015/01/21 00:00 [received]
PHST- 2015/04/13 00:00 [accepted]
PHST- 2015/05/27 06:00 [entrez]
PHST- 2015/05/27 06:00 [pubmed]
PHST- 2016/04/19 06:00 [medline]
PHST- 2015/05/26 00:00 [pmc-release]
AID - PONE-D-14-57446 [pii]
AID - 10.1371/journal.pone.0127319 [doi]
PST - epublish
SO  - PLoS One. 2015 May 26;10(5):e0127319. doi: 10.1371/journal.pone.0127319. 
      eCollection 2015.