Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice.

Yang, Zhenglin; Chen, Yali; Lillo, Concepcion; Chien, Jeremy; Yu, Zhengya; Michaelides, Michel; Klein, Martin; Howes, Kim A; Li, Yang; Kaminoh, Yuuki; Chen, Haoyu; Zhao, Chao; Chen, Yuhong; Al-Sheikh, Youssef Tawfik; Karan, Goutam; Corbeil, Denis; Escher, Pascal; Kamaya, Shin; Li, Chunmei; Johnson, Samantha; ... (2008). Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. Journal of clinical investigation, 118(8), pp. 2908-2916. American Society for Clinical Investigation 10.1172/JCI35891

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Familial macular degeneration is a clinically and genetically heterogeneous group of disorders characterized by progressive central vision loss. Here we show that an R373C missense mutation in the prominin 1 gene (PROM1) causes 3 forms of autosomal-dominant macular degeneration. In transgenic mice expressing R373C mutant human PROM1, both mutant and endogenous PROM1 were found throughout the layers of the photoreceptors, rather than at the base of the photoreceptor outer segments, where PROM1 is normally localized. Moreover, the outer segment disk membranes were greatly overgrown and misoriented, indicating defective disk morphogenesis. Immunoprecipitation studies showed that PROM1 interacted with protocadherin 21 (PCDH21), a photoreceptor-specific cadherin, and with actin filaments, both of which play critical roles in disk membrane morphogenesis. Collectively, our results identify what we believe to be a novel complex involved in photoreceptor disk morphogenesis and indicate a possible role for PROM1 and PCDH21 in macular degeneration.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Escher, Pascal

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

PD Dr. Pascal Escher

Date Deposited:

10 Jul 2017 15:40

Last Modified:

31 Jul 2017 08:31

Publisher DOI:

10.1172/JCI35891

PubMed ID:

18654668

BORIS DOI:

10.7892/boris.101776

URI:

https://boris.unibe.ch/id/eprint/101776

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