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

Zhenglin Yang, Yali Chen, Concepcion Lillo, Jeremy Chien, Zhengya Yu, Michel Michaelides, Martin Klein, Kim A. Howes, Yang Li, Yuuki Kaminoh, Haoyu Chen, Chao Zhao, Yuhong Chen, Youssef Tawfik Al-Sheikh, Goutam Karan, Denis Corbeil, Pascal Escher, Shin Kamaya, Chunmei Li, Samantha JohnsonJeanne M. Frederick, Yu Zhao, Changguan Wang, D. Joshua Cameron, Wieland B. Huttner, Daniel F. Schorderet, Frances L. Munier, Anthony T. Moore, David G. Birch, Wolfgang Baehr, David M. Hunt, David S. Williams, Kang Zhang

Research output: Contribution to journalArticlepeer-review

182 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2908-2916
Number of pages9
JournalJournal of Clinical Investigation
Issue number8
StatePublished - Aug 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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