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Publication
Altered Ocular Fibrillin Microfibril Composition in Mice With a Glaucoma-Causing
Mutation of Adamts10.
Authors Wu HJ, Mortlock DP, Kuchtey RW, Kuchtey J
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Investigative ophthalmology & visual science
Year 2021
Date Published 8/1/2021
Volume : Pages 62 : 26
PubMed Reference 34424262
Abstract Previously, we identified a G661R mutation of ADAMTS10 (a disintegrin-like and
metalloprotease with thrombospondin type 1 motif 10) as being disease causative
in a colony of Beagles with inherited primary open-angle glaucoma (POAG).
Mutations in ADAMTS10 are known to cause Weill-Marchesani syndrome (WMS), which
is also caused by mutations in the fibrillin-1 gene (FBN1), suggesting
functional linkage between ADAMTS10 and fibrillin-1, the principal component of
microfibrils. Here, we established a mouse line with the G661R mutation of
Adamts10 (Adamts10G661R/G661R) to determine if they develop features of WMS and
alterations of ocular fibrillin microfibrils., Intraocular pressure (IOP) was
measured using a TonoLab rebound tonometer. Central cornea thickness (CCT),
anterior chamber depth (ACD) and axial length (AL) of the eye were examined by
spectral-domain optical coherence tomography. Sagittal eye sections from mice at
postnatal day 10 (P10) and at 3 and 24 months of age were stained with
antibodies against fibrillin-1, fibrillin-2, and ADAMTS10., IOP was not elevated
in Adamts10G661R/G661R mice. Adamts10G661R/G661R mice had smaller bodies,
thicker CCT, and shallower ACD compared to wild-type mice but normal AL.
Adamts10G661R/G661R mice displayed persistent fibrillin-2 and enhanced
fibrillin-1 immunofluorescence in the lens zonules and in the hyaloid
vasculature and its remnants in the vitreous., Adamts10G661R/G661R mice
recapitulate the short stature and ocular phenotypes of WMS. The altered
fibrillin-1 and fibrillin-2 immunoactivity in Adamts10G661R/G661R mice suggests
that the G661R mutation of Adamts10 perturbs regulation of the fibrillin isotype
composition of microfibrils in the mouse eye.




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