title: Reduced corneal thickness and enlarged anterior chamber in a novel ColVIIIa2G257D mutant mouse.
abstract: OBJECTIVE
  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.
authors: Institute of Developmental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany. oliver.puk@helmholtz-muenchen.de
authors: Oliver
authors: O
authors: Puk
authors: Claudia
authors: C
authors: Dalke
authors: Julia
authors: J
authors: Calzada-Wack
authors: Nafees
authors: N
authors: Ahmad
authors: Matthias
authors: M
authors: Klaften
authors: Sibylle
authors: S
authors: Wagner
authors: Martin Hrabé
authors: MH
authors: de Angelis
authors: Jochen
authors: J
authors: Graw
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D000867:Anterior Chamber / Q000002:abnormalities* / Q000473:pathology; D024102:Collagen Type VIII / Q000235:genetics*; D003315:Cornea / Q000002:abnormalities* / Q000473:pathology; D004195:Disease Models, Animal; D005038:Ethylnitrosourea / Q000633:toxicity; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D008040:Genetic Linkage; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007368:Interferometry; D008027:Light; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats; D016297:Mutagenesis, Site-Directed; D009887:Ophthalmoscopy; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014792:Visual Acuity / Q000502:physiology
chemical_list: D000477:Alkylating Agents; C507463:Col8a2 protein, mouse; D024102:Collagen Type VIII; D005038:Ethylnitrosourea