Dataset Information

Proteomic profiling reveals central role of STAT signaling during retinal degeneration in the rd10 mouse model

ABSTRACT: The rd10 mouse is a model of retinitis pigmentosa characterized by the dysfunction of a rod-photoreceptor-specific phosphodiesterase. Compared to the rd1 mouse, retinal degeneration in the rd10 mouse begins later in age with a milder phenotype, making it ideal for investigating cell death and neuroprotective mechanisms. Alterations in the rd10 retina proteome at pre-, peak-, and post-degenerative time points were examined using a modified high-recovery filter-aided sample preparation (FASP) method and label-free mass spectrometry, generating a unique proteomic dataset on almost 3000 proteins. Our data confirmed a period of protein expression similar to age-matched wild-type mice pre-degeneration, with decreases in proteins associated with phototransduction and increases in signaling proteins at peak- and post-degenerative stages. 123 proteins were differentially expressed the rd10 retinae during peak-degeneration compared to wild-type mice. Network analysis separated these proteins into a cluster of downregulated photoreceptor proteins, and one of upregulated signaling proteins centered around GFAP, STAT3, and STAT1. This is the first study to identify alterations in STAT1 in the rd10 mouse, which were confirmed with gene expression and immunoblotting experiments. This finding proves the efficacy of our approach, and that this dataset could serve as an information source for protein alterations in retinal degeneration.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Retina

DISEASE(S): Retinitis Pigmentosa

SUBMITTER: Juliane Merl-Pham

LAB HEAD: Stefanie M. Hauck

PROVIDER: PXD002584 | Pride | 2016-03-21

REPOSITORIES: Pride

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Publications

Proteomic Profiling Suggests Central Role Of STAT Signaling during Retinal Degeneration in the rd10 Mouse Model.

Ly Alice A Merl-Pham Juliane J Priller Markus M Gruhn Fabian F Senninger Nicole N Ueffing Marius M Hauck Stefanie M SM

Journal of proteome research 20160314 4

The rd10 mouse is a model of retinitis pigmentosa characterized by the dysfunction of a rod-photoreceptor-specific phosphodiesterase. Compared to the rd1 mouse, retinal degeneration in the rd10 mouse begins later in age with a milder phenotype, making it ideal for investigating cell death and neuroprotective mechanisms. Alterations in the rd10 retina proteome at pre-, peak-, and postdegenerative time points were examined using a modified high-recovery filter-aided sample preparation (FASP) metho ...[more]

PMID: 26939627

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Project description:Retinal degeneration is the leading cause of irreversible blindness. Retinitis pigmentosa (RP) is a genetically heterogenous group of diseases. In the United States, approximately one in 4000 individuals is affected. RP begins with the loss of night vision due to the loss of rod photoreceptor cells. The disease progresses slowly with the loss of peripheral vision, and eventually leads to complete debilitating and irreversible blindness. The first mutation associated with human RP was identified in the gene encoding rhodopsin, the G-protein coupled receptor of rod photoreceptor cells. Mutations within the rhodopsin gene account for significant portion of RP cases. Specifically, mutations of the proline at residue 347 in rhodopsin have been linked to human RP. We are fortunate to have access to the P347S rhodopsin mutant mice. These mice represent an excellent transgenic mouse model of retinal degeneration. The P347S rhodopsin mutation is one of the best studied mutations, yet the mechanism by which the mutation causes degeneration is still unknown. One study has demonstrated that galectin-1 plays a role in degeneration of neuronal processes (1) and another study has shown that expression level of galectin-3 is elevated in retinas of patients with age-related macular degeneration. These studies in conjunction with the availibility of the P347S mutant mice have provided impetus to examine the pathogenesis of retinal degeneration in the context of the possible role of glycans and glycan-binding proteins. The time course of photoreceptor degeneration in the P347S mouse model has been carefully studied. In these mice, degeneration is barely detectable at 1 month of age, yet biochemical evidence suggests that the rod photoreceptor cells have already begun to die. At 4 months of age, approximately half of the rod photoreceptor cells have degenerated. To distinguish involvement of glycogens at the various stages of retinal degeneration, we have collected retinas of wild type and the mutant mice at four time points (1, 2, 3, and 4 months of age). This will allow us to identify the genes that target early, mid- and late stages of the retinal degeneration process. Thus we request the analysis of total 24 samples as specified below: Age Group (months) Mice No of samples at each time point 1 Wild type 3 2 Wild type 3 3 Wild type 3 4 Wild type 3 1 P347S 3 2 P347S 3 3 P347S 3 4 P347S 3 Total 24.

Dataset Information

Proteomic profiling reveals central role of STAT signaling during retinal degeneration in the rd10 mouse model

Publications

Proteomic Profiling Suggests Central Role Of STAT Signaling during Retinal Degeneration in the rd10 Mouse Model.

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