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Parry, D.A.* ; Toomes, C.* ; Bida, L.* ; Danciger, M.* ; Towns, K.V.* ; McKibbin, M.* ; Jacobson, S.G.* ; Logan, C.V.* ; Ali, M.* ; Bond, J.* ; Chance, R.* ; Swendeman, S.* ; Daniele, L.L.* ; Springell, K.* ; Adams, M.* ; Johnson, C.A.* ; Booth, A.P.* ; Jafari, H.* ; Rashid, Y.* ; Banin, E.* ; Strom, T.M. ; Farber, D.B.* ; Sharon, D.* ; Blobel, C.P.* ; Pugh, E.N.* ; Pierce, E.A.* ; Inglehearn, C.F.*

Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice.

Am. J. Hum. Genet. 84, 683-691 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Cone-rod dystrophy (CRD) is an inherited progressive retinal dystrophy affecting the function of cone and rod photoreceptors. By autozygosity mapping, we identified null mutations in the ADAM metallopeptidase domain 9 (ADAM9) gene in four consanguineous families with recessively inherited early-onset CRD. We also found reduced photoreceptor responses in Adam9 knockout mice, previously reported to be asymptomatic. In 12-month-old knockout mice, photoreceptors appear normal, but the apical processes of the retinal pigment epithelium (RPE) cells are disorganized and contact between photoreceptor outer segments (POSs) and the RPE apical surface is compromised. In 20-month-old mice, there is clear evidence of progressive retinal degeneration with disorganized POS and thinning of the outer nuclear layer (ONL) in addition to the anomaly at the POS-RPE junction. RPE basal deposits and macrophages were also apparent in older mice. These findings therefore not identify ADAM9 as a CRD gene but also identify a form of pathology wherein retinal disease first manifests at the POS-RPE junction.
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Publication type Article: Journal article
Document type Scientific Article
Keywords age-related maculopathy; macular degeneration; fundus dystrophy; gene; mutations; susceptibility; disintegrin; expression; locus; integrin
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Journal American Journal of Human Genetics, The
Quellenangaben Volume: 84, Issue: 5, Pages: 683-691 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)