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Yan, X.* ; Atorf, J.* ; Ramos, D.* ; Thiele, F. ; Weber, S. ; Dalke, C. ; Sun, M. ; Puk, O. ; Michel, D. ; Fuchs, H. ; Klaften, M. ; Przemeck, G.K.H. ; Sabrautzki, S. ; Favor, J. ; Ruberte, J.* ; Kremers, J.* ; Hrabě de Angelis, M. ; Graw, J. ; German Mouse Clinic Consortium*

Mutation in Bmpr1b leads to optic disc coloboma and ventral retinal gliosis in mice.

Invest. Ophthalmol. Vis. Sci. 61:44 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
PURPOSE. The clinical phenotype of retinal gliosis occurs in different forms; here, we characterize one novel genetic feature, (i.e., signaling via BMP-receptor 1b).METHODS. Mouse mutants were generated within a recessive ENU mutagenesis screen; the underlying mutation was identified by linkage analysis and Sanger sequencing. The eye phenotype was characterized by fundoscopy, optical coherence tomography, optokinetic drum, electroretinography, and visual evoked potentials, by histology, immunohistology, and electron-microscopy.RESULTS. The mutation affects intron 10 of the Bmpr1b gene, which is causative for skipping of exon 10. The expression levels of pSMAD1/5/8 were reduced in the mutant retina. The loss of BMPR1B-mediated signaling leads to optic nerve coloboma, gliosis in the optic nerve head and ventral retina, defective optic nerve axons, and irregular retinal vessels. The ventral retinal gliosis is proliferative and hypertrophic, which is concomitant with neuronal delamination and the reduction of retinal ganglion cells (RGCs); it is dominated by activated astrocytes overexpressing PAX2 and SOX2 but not PAX6, indicating that they may retain properties of gliogenic precursor cells. The expression pattern of PAX2 in the optic nerve head and ventral retina is altered during embryonic development. These events finally result in reduced electrical transmission of the retina and optic nerve and significantly reduced visual acuity.CONCLUSIONS. Our study demonstrates that BMPR1B is necessary for the development of the optic nerve and ventral retina. This study could also indicate a new mechanism in the formation of retinal gliosis; it opens new routes for its treatment eventually preventing scar formation in the retina.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Bmpr1b ; Mouse Model ; Retinal Gliosis ; Optic Nerve Coloboma; Bone Morphogenetic Protein-7; Reactive Gliosis; Eye Development; Pax2 Mutation; Mutant Mice; Genome-wide; Cell Fate; Mouse; Differentiation; Astrocytes
ISSN (print) / ISBN 0146-0404
e-ISSN 1552-5783
Journal Investigative Ophthalmology & Visual Science, IOVS
Quellenangaben Volume: 61, Issue: 2, Pages: , Article Number: 44 Supplement: ,
Publisher Association for Research in Vision and Ophthalmology (ARVO)
Publishing Place 12300 Twinbrook Parkway, Rockville, Md 20852-1606 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
CF Comparative Medicine (CF-Comparative Medicine)
Institute of Human Genetics (IHG)