title: Heterozygote Wdr36-deficient mice do not develop glaucoma.
abstract: There is an ongoing controversy regarding the role of WDR36 sequence variants in the pathogenesis of primary open-angle glaucoma (POAG). WDR36 is a nucleolar protein involved in the maturation of 18S rRNA. The function of WDR36 is essential as homozygous Wdr36-deficient mouse embryos die before reaching the blastocyst stage. Here we provide a detailed analysis of the phenotype of heterozygous Wdr36-deficient mice. Loss of one Wdr36 allele causes a substantial reduction in the expression of Wdr36 mRNA. In the eyes of Wdr36(+/-) animals, the structure of the tissues involved in aqueous humor circulation and of the optic nerve head are not different from that of control littermates. In addition, one-year-old Wdr36(+/-) animals do not differ from wild-type animals with regards to intraocular pressure and number of optic nerve axons. The susceptibility of retinal ganglion cells to excitotoxic damage induced by NMDA is similar in Wdr36(+/-) and wild-type animals. Moreover, the amount of optic nerve axonal damage induced by high IOP is not different between Wdr36(+/-) and wild-type mice. Transgenic overexpression of mutated Del605-607 Wdr36 in Wdr36(+/-) animals does not cause changes in the number of optic nerve axons or susceptibility to excitotoxic damage. In addition, analysis of 18S rRNA maturation in Del605-607 Wdr36(+/-) or Wdr36(+/-) mice does not show obvious differences in rRNA processing or in the amounts of precursor forms when compared to wild-type animals. Our data obtained in Wdr36(+/-) mice do not support the assumption of a causative role for WDR36 in the pathogenesis of POAG.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gallenberger
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kroeber
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany.
authors.forename: Loreen
authors.initials: L
authors.lastname: März
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Koch
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Braunger
authors.affiliation: Molecular & Cellular Biology Division, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, D-93053 Regensburg, Germany. Electronic address: ernst.tamm@vkl.uni-regensburg.de.
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
mesh_terms: D000483:Alleles; D000818:Animals; D001369:Axons / Q000473:pathology; D015152:Blotting, Northern; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D007429:Intraocular Pressure; D019656:Loss of Heterozygosity / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000633:toxicity; D009901:Optic Nerve Diseases / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012307:Risk Factors; D014065:Tonometry, Ocular
chemical_list: D005136:Eye Proteins; D012333:RNA, Messenger; C554605:WDR36 protein, mouse; D016202:N-Methylaspartate
keywords: Animal model; Genetics; Primary open-angle glaucoma