title: Induction of STAT3-related genes in fast degenerating cone photoreceptors of cpfl1 mice.
abstract: Cone dystrophies are genetic diseases characterized by loss of cone photoreceptor function and severe impairment of daylight vision. Loss of function is accompanied by a progressive degeneration of cones limiting potential therapeutic interventions. In this study we combined microarray-based gene-expression analysis with electroretinography and immunohistochemistry to characterize the pathological processes in the cone photoreceptor function loss 1 (cpfl1) mouse model. The cpfl1-mouse is a naturally arising mouse mutant with a loss-of-function mutation in the cone-specific Pde6c gene. Cpfl1-mice displayed normal rod-specific light responses while cone-specific responses were strongly diminished. Despite the lack of a general retinal degeneration, the cone-specific functional defect resulted in a marked activation of GFAP, a hallmark of Müller-cell gliosis. Microarray-based network-analysis confirmed activation of Müller-glia-specific transcripts. Unexpectedly, we found up-regulation of the cytokine LIF and the anti-apoptotic transcription factor STAT3 in cpfl1 cone photoreceptors. We postulate that STAT3-related pathways are induced in cpfl1 cone photoreceptors to counteract degeneration.
authors.affiliation: Microarray Facility, Department of Medical Genetics, University of Tuebingen, Calwerstr. 7, 72076, Tuebingen, Germany. karin.schaeferhoff@med.uni-tuebingen.de
authors.forename: K
authors.initials: K
authors.lastname: Schaeferhoff
authors.forename: S
authors.initials: S
authors.lastname: Michalakis
authors.forename: N
authors.initials: N
authors.lastname: Tanimoto
authors.forename: M D
authors.initials: MD
authors.lastname: Fischer
authors.forename: E
authors.initials: E
authors.lastname: Becirovic
authors.forename: S C
authors.initials: SC
authors.lastname: Beck
authors.forename: G
authors.initials: G
authors.lastname: Huber
authors.forename: N
authors.initials: N
authors.lastname: Rieger
authors.forename: O
authors.initials: O
authors.lastname: Riess
authors.forename: B
authors.initials: B
authors.lastname: Wissinger
authors.forename: M
authors.initials: M
authors.lastname: Biel
authors.forename: M W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: M
authors.initials: M
authors.lastname: Bonin
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
references.citation: Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1516-24
references.pmid: 15790924
references.citation: J Biol Chem. 2003 Jun 6;278(23):21070-5
references.pmid: 12665506
references.citation: BMC Neurosci. 2005 Nov 30;6:69
references.pmid: 16318630
references.citation: J Neurochem. 2008 May;105(3):784-96
references.pmid: 18088375
references.citation: J Mol Biol. 2008 Mar 14;377(1):28-46
references.pmid: 18237746
references.citation: J Cell Physiol. 2003 Nov;197(2):157-68
references.pmid: 14502555
references.citation: Circ Res. 2006 Apr 14;98(7):913-22
references.pmid: 16527988
references.citation: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3095-9
references.pmid: 18378583
references.citation: FASEB J. 2006 Nov;20(13):2411-3
references.pmid: 16966486
references.citation: Am J Hum Genet. 2002 Aug;71(2):422-5
references.pmid: 12077706
references.citation: Invest Ophthalmol Vis Sci. 2001 Feb;42(2):506-13
references.pmid: 11157890
references.citation: Mol Cell Biol. 1998 Apr;18(4):2108-17
references.pmid: 9528783
references.citation: Mol Biol Cell. 2002 Apr;13(4):1274-81
references.pmid: 11950938
references.citation: Invest Ophthalmol Vis Sci. 2006 Nov;47(11):5017-21
references.pmid: 17065522
references.citation: J Biol Chem. 2008 Sep 5;283(36):24561-70
references.pmid: 18614536
references.citation: Front Biosci (Landmark Ed). 2009 Jan 01;14(7):2730-7
references.pmid: 19273231
references.citation: Nucleic Acids Res. 2002 May 1;30(9):e36
references.pmid: 11972351
references.citation: J Neurochem. 2003 Apr;85(1):73-81
references.pmid: 12641728
references.citation: Mol Cell Neurosci. 2006 Sep;33(1):81-7
references.pmid: 16870469
references.citation: Int Immunol. 2006 Jul;18(7):1079-89
references.pmid: 16702165
references.citation: Science. 1997 Sep 12;277(5332):1630-5
references.pmid: 9287210
references.citation: J Neurochem. 1997 Apr;68(4):1413-23
references.pmid: 9084411
references.citation: Nat Genet. 2001 Sep;29(1):70-4
references.pmid: 11528395
references.citation: Mol Vis. 2004 Dec 22;10:973-86
references.pmid: 15623987
references.citation: J Neurosci. 2008 Dec 17;28(51):13765-74
references.pmid: 19091967
references.citation: J Cell Sci. 2000 Aug;113 ( Pt 16):2813-9
references.pmid: 10910765
references.citation: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4409-16
references.pmid: 16303927
references.citation: Mol Endocrinol. 2008 Dec;22(12):2677-88
references.pmid: 18927239
references.citation: Vision Res. 2002 Feb;42(4):517-25
references.pmid: 11853768
references.citation: Cardiovasc Res. 2005 Feb 1;65(2):428-35
references.pmid: 15639482
references.citation: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):927-36
references.pmid: 10711715
references.citation: J Neurosci. 2005 May 4;25(18):4540-9
references.pmid: 15872101
references.citation: Cancer Res. 2004 Oct 1;64(19):6924-33
references.pmid: 15466183
references.citation: Am J Hum Genet. 2009 Aug;85(2):240-7
references.pmid: 19615668
references.citation: PLoS One. 2009 Oct 19;4(10):e7507
references.pmid: 19838301
references.citation: Oncogene. 2004 Jan 8;23(1):168-78
references.pmid: 14712222
references.citation: Eur J Hum Genet. 2005 Mar;13(3):302-8
references.pmid: 15657609
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7553-7
references.pmid: 10377453
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19581-6
references.pmid: 19887631
references.citation: Immunity. 2005 Nov;23(5):491-502
references.pmid: 16286017
references.citation: Curr Eye Res. 2002 Apr;24(4):305-12
references.pmid: 12324870
references.citation: Doc Ophthalmol. 2004 Mar;108(2):107-14
references.pmid: 15455793
references.citation: J Neurosci Res. 2005 Jul 15;81(2):163-71
references.pmid: 15948155
references.citation: J Biol Chem. 2004 May 7;279(19):19936-47
references.pmid: 14996842
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16158-63
references.pmid: 17911267
references.citation: J Neurosci. 1992 Oct;12(10):3968-78
references.pmid: 1403094
references.citation: Endocr Relat Cancer. 2005 Jun;12(2):319-34
references.pmid: 15947106