Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 118, Issue 8, Pages 2908-2916Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI35891
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Funding
- NCRR NIH HHS [M01 RR000064, M01-RR00064] Funding Source: Medline
- NEI NIH HHS [P30 EY012598, P30 EY014800, EY05235, P30EY014800, R01 EY005235, R01EY14428, P30EY12598, R01 EY007042, R01EY07042, R01 EY007042-22, R01 EY008123, R01 EY014428, R01 EY08123, R01EY14448, R01 EY014448] Funding Source: Medline
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Familial macular degeneration is a clinically and genetically heterogeneous group of disorders characterized by progressive central visionloss. 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 PROM I 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.
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