Abstract
Rhodopsin (Pro347Leu) transgenic pigs are recognized to be an excellent model for the human disease, retinitis pigmentosa. First published in 1997, the rhodopsin transgenic pigs have been maintained since that time at North Carolina State University by outcrossing hemizygous boars to unrelated sows. Nine generations of outcrossing have been completed. Since the genetic background of these pigs has undoubtedly changed, the question of the current phenotype of the transgenic pigs is relevant for their future use. Age-matched transgenic and non-transgenic eyes were submitted for histological analysis using hematoxylin and eosin staining. Even by 2 weeks of age, significant thinning of the outer nuclear layer of photoreceptors was observed. For ages 3 and 4 weeks, thinning was noted similar to that of 2 weeks of age. By 6 weeks of age outer nuclear layer thinning was greater than that of earlier age. At 11 weeks of age, most of the rods have degenerated leaving only a few layers of cones. In all, the phenotype, based on assessment of photoreceptor degeneration, is similar to that of the first description of the transgenic animals. As such the Pro347Leu rhodopsin transgenic pigs have exhibited phenotypic stability through generations of outcrossing and can be used confidently in future studies of the type of retinal degeneration seen with retinitis pigmentosa.
This is a preview of subscription content, log in via an institution to check access.
References
Banin E, Cideciyan AV, Aleman TS, Petters RM, Wong F, Milam AH, Jacobson SG (1999) Retinal rod photoreceptor-specific gene mutation perturbs cone pathway development. Neuron 23(3):549–557
Beauchemin ML (1974) The fine structure of the pig’s retina. Albrecht Von Graefes Arch Klin Exp Ophthalmol 190(1):27–45
Blackmon SM, Peng YW, Hao Y, Moon SJ, Oliveira LB, Tatebayashi M, Petters RM, Wong F (2000) Early loss of synaptic protein PSD-95 from rod terminals of rhodopsin P347L transgenic porcine retina. Brain Res 885(1):53–61
Chandler MJ, Smith PJ, Samuelson DA, MacKay EO (1999) Photoreceptor density of the domestic pig retina. Vet Ophthalmol 2(3):179–184
Cho HJ, Seiberg M, Georgoff I, Teresky AK, Marks JR, Levine AJ (1989) Impact of the genetic background of transgenic mice upon the formation and timing of choroid plexus papillomas. J Neurosci Res 24(1):115–122. doi:10.1002/jnr.490240116
Gerke CG Jr, Hao Y, Wong F (1995) Topography of rods and cones in the retina of the domestic pig. Hong Kong Med J 1:302–308
Ghosh F, Wong F, Johansson K, Bruun A, Petters RM (2004) Transplantation of full-thickness retina in the rhodopsin transgenic pig. Retina 24(1):98–109
Ghosh F, Engelsberg K, English RV, Petters RM (2007) Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol 245(6):835–846
Hafezi F, Grimm C, Simmen BC, Wenzel A, Reme CE (2000) Molecular ophthalmology: an update on animal models for retinal degenerations and dystrophies. Br J Ophthalmol 84(8):922–927
Hendrickson A, Hicks D (2002) Distribution and density of medium- and short-wavelength selective cones in the domestic pig retina. Exp Eye Res 74(4):435–444
Huang Y, Cideciyan AV, Aleman TS, Banin E, Huang J, Syed NA, Petters RM, Wong F, Milam AH, Jacobson SG (2000) Optical coherence tomography (OCT) abnormalities in rhodopsin mutant transgenic swine with retinal degeneration. Exp Eye Res 70(2):247–251
Kraft TW, Allen D, Petters RM, Hao Y, Peng YW, Wong F (2005) Altered light responses of single rod photoreceptors in transgenic pigs expressing P347L or P347S rhodopsin. Mol Vis 11:1246–1256
Li ZY, Wong F, Chang JH, Possin DE, Hao Y, Petters RM, Milam AH (1998) Rhodopsin transgenic pigs as a model for human retinitis pigmentosa. Invest Ophthalmol Vis Sci 39(5):808–819
Mahmoud TH, McCuen BW 2nd, Hao Y, Moon SJ, Tatebayashi M, Stinnett S, Petters RM, Wong F (2003) Lensectomy and vitrectomy decrease the rate of photoreceptor loss in rhodopsin P347L transgenic pigs. Graefes Arch Clin Exp Ophthalmol 241(4):298–308
Ng YF, Chan HH, Chu PH, To CH, Gilger BC, Petters RM, Wong F (2008) Multifocal electroretinogram in rhodopsin P347L transgenic pigs. Invest Ophthalmol Vis Sci 49(5):2208–2215
Peng YW, Hao Y, Petters RM, Wong F (2000) Ectopic synaptogenesis in the mammalian retina caused by rod photoreceptor-specific mutations. Nat Neurosci 3(11):1121–1127
Petters RM, Alexander CA, Wells KD, Collins EB, Sommer JR, Blanton MR, Rojas G, Hao Y, Flowers WL, Banin E, Cideciyan AV, Jacobson SG, Wong F (1997) Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nat Biotechnol 15(10):965–970
Shen J, Yang X, Dong A, Petters RM, Peng YW, Wong F, Campochiaro PA (2005) Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa. J Cell Physiol 203(3):457–464
Tso MO, Li WW, Zhang C, Lam TT, Hao Y, Petters RM, Wong F (1997) A pathologic study of degeneration of the rod and cone populations of the rhodopsin Pro347Leu transgenic pigs. Trans Am Ophthalmol Soc 95:467–479; discussion 479–483
Wolfer DP, Lipp HP (2000) Dissecting the behaviour of transgenic mice: is it the mutation, the genetic background, or the environment? Exp Physiol 85(6):627–634
Wolfer DP, Muller U, Stagliar M, Lipp HP (1997) Assessing the effects of the 129/Sv genetic background on swimming navigation learning in transgenic mutants: a study using mice with a modified beta-amyloid precursor protein gene. Brain Res 771(1):1–13. doi:S0006-8993(97)00673-2[pii]
Acknowledgments
We thank Mr. Kent Gray for statistical consultation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sommer, J.R., Wong, F. & Petters, R.M. Phenotypic stability of Pro347Leu rhodopsin transgenic pigs as indicated by photoreceptor cell degeneration. Transgenic Res 20, 1391–1395 (2011). https://doi.org/10.1007/s11248-011-9491-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11248-011-9491-0