| First Author | Dubail J | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 33974 | PubMed ID | 27687499 |
| Mgi Jnum | J:253196 | Mgi Id | MGI:6101931 |
| Doi | 10.1038/srep33974 | Citation | Dubail J, et al. (2016) Impaired ADAMTS9 secretion: A potential mechanism for eye defects in Peters Plus Syndrome. Sci Rep 6:33974 |
| abstractText | Peters Plus syndrome (PPS), a congenital disorder of glycosylation, results from recessive mutations affecting the glucosyltransferase B3GLCT, leading to congenital corneal opacity and diverse extra-ocular manifestations. Together with the fucosyltransferase POFUT2, B3GLCT adds Glucosebeta1-3Fucose disaccharide to a consensus sequence in thrombospondin type 1 repeats (TSRs) of several proteins. Which of these target proteins is functionally compromised in PPS is unknown. We report here that haploinsufficiency of murine Adamts9, encoding a secreted metalloproteinase with 15 TSRs, leads to congenital corneal opacity and Peters anomaly (persistent lens-cornea adhesion), which is a hallmark of PPS. Mass spectrometry of recombinant ADAMTS9 showed that 9 of 12 TSRs with the O-fucosylation consensus sequence carried the Glucosebeta1-3Fucose disaccharide and B3GLCT knockdown reduced ADAMTS9 secretion in HEK293F cells. Together, the genetic and biochemical findings imply a dosage-dependent role for ADAMTS9 in ocular morphogenesis. Reduced secretion of ADAMTS9 in the absence of B3GLCT is proposed as a mechanism of Peters anomaly in PPS. The functional link between ADAMTS9 and B3GLCT established here also provides credence to their recently reported association with age-related macular degeneration. |
