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Puk, O. ; Dalke, C. ; Calzada-Wack, J. ; Ahmad, N. ; Klaften, M. ; Wagner, S. ; Hrabě de Angelis, M. ; Graw, J.

Reduced corneal thickness and enlarged anterior chamber in a novel ColVIIIa2(G257D) mutant mouse.

Invest. Ophthalmol. Vis. Sci. 50, 5653-5661 (2009)
DOI PMC
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
The purpose of this study was the morphologic and genetic characterization of the novel eye size mutant Aca23 in the mouse. METHODS: The eyes of the mutants were characterized in vivo by optical low-coherence interferometry, Scheimpflug imaging, and funduscopy. Visual acuity was examined using a virtual optomotor system. Morphology was studied by histology, in situ hybridization, and immunohistochemistry. Linkage analysis was performed using genomewide scans with single nucleotide polymorphisms and microsatellite markers. RESULTS: Aca23 is a new semidominant eye size mutant that was discovered in an ENU mutagenesis screen. The phenotype includes increased anterior chamber depths, extended axial lengths, and reduced thickness of corneal layers. Aca23 was mapped to chromosome 4. A G-->A point mutation was identified at cDNA position 770 of Col8a2 encoding collagen VIII alpha2. The transition results in a G257D amino acid exchange affecting a highly conserved glycine residue in the collagenous domain. Proliferation of corneal endothelium, eye fundus, and visual acuity are not affected. CONCLUSIONS: The mouse mutant Aca23 described here offers the first point mutation of the Col8a2 gene in the mouse. The results of this study suggest that a functional collagen VIII alpha2 is essential for the correct assembly of the Descemet's membrane and for corneal stability. Aca23 might be used as a novel model for keratoglobus.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords rhizomelic chondrodysplasia punctata; posterior polymorphous dystrophy; sox2 anophthalmia syndrome; viii collagen; micro-syndrome; pts2 receptor; endothelial dystrophy; descemets-membrane; gene-mutations; large-scale
ISSN (print) / ISBN 0146-0404
e-ISSN 1552-5783
Journal Investigative Ophthalmology & Visual Science, IOVS
Quellenangaben Volume: 50, Issue: 12, Pages: 5653-5661 Article Number: , Supplement: ,
Publisher Association for Research in Vision and Ophthalmology (ARVO)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Institute of Pathology (PATH)