Altered Ocular Fibrillin Microfibril Composition in Mice With a Glaucoma-Causing Mutation of Adamts10

Invest Ophthalmol Vis Sci. 2021 Aug 2;62(10):26. doi: 10.1167/iovs.62.10.26.


Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS Proteins / genetics*
  • ADAMTS Proteins / metabolism
  • Animals
  • Anterior Chamber / metabolism*
  • DNA / genetics*
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Female
  • Fibrillins / metabolism*
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / metabolism
  • Glaucoma, Open-Angle / physiopathology
  • Male
  • Mice
  • Microfibrils / metabolism*
  • Mutation*
  • Signal Transduction


  • Fibrillins
  • DNA
  • ADAMTS Proteins
  • ADAMTS10 protein, mouse