Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice.

Human Molecular Genetics
Zai-Long ChiTakeshi Iwata

Abstract

Primary open-angle glaucoma (POAG) is one of the three principal subtypes of glaucoma and among the leading cause of blindness worldwide. POAG is defined by cell death of the retinal ganglion cells (RGCs) and surrounding neuronal cells at higher or normal intraocular pressure (IOP). Coded by one of the three genes responsible for POAG, WD repeat-containing protein 36 (WDR36) has two domains with a similar folding. To address whether WDR36 is functionally important in the retina, we developed four transgenic mice strains overexpressing a wild-type (Wt) and three mutant variants of D606G, deletion of amino acids at positions 605-607 (Del605-607) and at 601-640 (Del601-640) equivalent to the location of the D658G mutation observed in POAG patients. A triple amino acid deletion of mouse Wdr36 at positions 605-607 corresponding to the deletion at positions 657-659 in humans developed progressive retinal degeneration at the peripheral retina with normal IOP. RGCs and connecting amacrine cell synapses were affected at the peripheral retina. Axon outgrowth rate of cultured RGC directly isolated from transgenic animal was significantly reduced by the Wdr36 mutation compared with Wt. Molecular modeling of wild and mutant mouse Wdr36 reve...Continue Reading

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Citations

May 13, 2011·Eye·J H Fingert
Nov 22, 2013·Japanese Journal of Ophthalmology·Mitsuko Takamoto, Makoto Araie
Aug 30, 2011·Experimental Eye Research·Yutao Liu, R Rand Allingham
Jun 28, 2015·Experimental Eye Research·Kimberly A FernandesRichard T Libby
Nov 19, 2013·Biochimica Et Biophysica Acta·Samuel B Sondalle, Susan J Baserga
Sep 24, 2013·Progress in Retinal and Eye Research·Sarah F JanssenArthur A B Bergen
Sep 28, 2014·Experimental Eye Research·Martin GallenbergerErnst R Tamm
Jun 29, 2016·Eye and Vision·Yelena BykhovskayaYaron S Rabinowitz
Jul 7, 2011·Current Opinion in Ophthalmology·Arif O Khan
Jun 18, 2020·International Journal of Molecular Sciences·Wioletta Rozpędek-KamińskaIreneusz Majsterek
Jan 18, 2019·Experimental and Therapeutic Medicine·Alexandra TrivliEfstathios T Detorakis
Jan 1, 2015·Journal of Experimental Neuroscience·Katie L Pennington, Margaret M DeAngelis

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Methods Mentioned

BETA
transgenic
biopsies
PCR
fluorescence laser

Software Mentioned

Look
Image J
SMART
Phyre
REPRO

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