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Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice
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-onse...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Elsevier
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681008/ https://www.ncbi.nlm.nih.gov/pubmed/19409519 http://dx.doi.org/10.1016/j.ajhg.2009.04.005 |
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author | Parry, David A. Toomes, Carmel Bida, Lina Danciger, Michael Towns, Katherine V. McKibbin, Martin Jacobson, Samuel G. Logan, Clare V. Ali, Manir Bond, Jacquelyn Chance, Rebecca Swendeman, Steven Daniele, Lauren L. Springell, Kelly Adams, Matthew Johnson, Colin A. Booth, Adam P. Jafri, Hussain Rashid, Yasmin Banin, Eyal Strom, Tim M. Farber, Debora B. Sharon, Dror Blobel, Carl P. Pugh, Edward N. Pierce, Eric A. Inglehearn, Chris F. |
author_facet | Parry, David A. Toomes, Carmel Bida, Lina Danciger, Michael Towns, Katherine V. McKibbin, Martin Jacobson, Samuel G. Logan, Clare V. Ali, Manir Bond, Jacquelyn Chance, Rebecca Swendeman, Steven Daniele, Lauren L. Springell, Kelly Adams, Matthew Johnson, Colin A. Booth, Adam P. Jafri, Hussain Rashid, Yasmin Banin, Eyal Strom, Tim M. Farber, Debora B. Sharon, Dror Blobel, Carl P. Pugh, Edward N. Pierce, Eric A. Inglehearn, Chris F. |
author_sort | Parry, David A. |
collection | PubMed |
description | 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 only identify ADAM9 as a CRD gene but also identify a form of pathology wherein retinal disease first manifests at the POS-RPE junction. |
format | Text |
id | pubmed-2681008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-26810082009-08-18 Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice Parry, David A. Toomes, Carmel Bida, Lina Danciger, Michael Towns, Katherine V. McKibbin, Martin Jacobson, Samuel G. Logan, Clare V. Ali, Manir Bond, Jacquelyn Chance, Rebecca Swendeman, Steven Daniele, Lauren L. Springell, Kelly Adams, Matthew Johnson, Colin A. Booth, Adam P. Jafri, Hussain Rashid, Yasmin Banin, Eyal Strom, Tim M. Farber, Debora B. Sharon, Dror Blobel, Carl P. Pugh, Edward N. Pierce, Eric A. Inglehearn, Chris F. Am J Hum Genet Report 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 only identify ADAM9 as a CRD gene but also identify a form of pathology wherein retinal disease first manifests at the POS-RPE junction. Elsevier 2009-05-15 /pmc/articles/PMC2681008/ /pubmed/19409519 http://dx.doi.org/10.1016/j.ajhg.2009.04.005 Text en © 2009 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. https://creativecommons.org/licenses/by/3.0/This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Report Parry, David A. Toomes, Carmel Bida, Lina Danciger, Michael Towns, Katherine V. McKibbin, Martin Jacobson, Samuel G. Logan, Clare V. Ali, Manir Bond, Jacquelyn Chance, Rebecca Swendeman, Steven Daniele, Lauren L. Springell, Kelly Adams, Matthew Johnson, Colin A. Booth, Adam P. Jafri, Hussain Rashid, Yasmin Banin, Eyal Strom, Tim M. Farber, Debora B. Sharon, Dror Blobel, Carl P. Pugh, Edward N. Pierce, Eric A. Inglehearn, Chris F. Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice |
title | Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice |
title_full | Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice |
title_fullStr | Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice |
title_full_unstemmed | Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice |
title_short | Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice |
title_sort | loss of the metalloprotease adam9 leads to cone-rod dystrophy in humans and retinal degeneration in mice |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681008/ https://www.ncbi.nlm.nih.gov/pubmed/19409519 http://dx.doi.org/10.1016/j.ajhg.2009.04.005 |
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