Reduced corneal thickness and enlarged anterior chamber in a novel ColVIIIa2G257D mutant mouse
Oliver Puk 1*,
Claudia Dalke 2,
Julia Calzada-Wack 3,
Nafees Ahmad 4,
Matthias Klaften 5,
Sibylle Wagner 5,
Martin Hrabé de Angelis 6,
and
Jochen Graw 7
1 Institute of Developmental Genetics, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, Neuherberg, Bayern, 85764, Germany
2 Institute of Developmental Genetics, Helmholtz Zentrum München, München, Bayern, Germany; Institute of Radiation Biology, Helmholtz Zentrum München, München, Bayern, Germany
3 Institute of Pathology, Helmholtz Zentrum München, München, Bayern, Germany
4 Institute of Developmental Genetics, Helmholtz Zentrum München, München, Germany
5 Institute of Experimental Genetics, Helmholtz Zentrum München, München, Bayern, Germany
6 Institute of Experimental Genetics, Helmholtz Zentrum München, München, Bayern, Germany; Experimental Genetics, Technical University Munich, Center of Life and Food Sciences, Freising-Weihenstephan, Germany
7 Institute of Developmental Genetics, Helmholtz Zentrum München, München, Bayern, Germany; Institute of Developmental Genetics, Technical University Munich, München, Bayern, Germany
* To whom correspondence should be addressed. E-mail: oliver.puk{at}gsf.de.
 |
Abstract |
|---|
Purpose. The purpose of this study was the morphological 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 genome-wide scans with single nucleotide polymorphisms and microsatellite markers.
Results. Aca23 is a new semidominant eye size mutant, which 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 
2. 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 2 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.
Key Words:
corneal thinning, collagen, Descemet's membrane, keratoglobus, macrophthalmia
