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Molecular and Cellular Biology, February 2008, p. 949-957, Vol. 28, No. 3
0270-7306/08/$08.00+0     doi:10.1128/MCB.00354-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Primary Ciliary Dyskinesia in Mice Lacking the Novel Ciliary Protein Pcdp1 ^,

Department of Pathology, Children's Hospital Boston and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115,¹ Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115,² Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198³

Received 27 February 2007/ Returned for modification 11 May 2007/ Accepted 5 November 2007

Primary ciliary dyskinesia (PCD) results from ciliary dysfunction and is commonly characterized by sinusitis, male infertility, hydrocephalus, and situs inversus. Mice homozygous for the nm1054 mutation develop phenotypes associated with PCD. On certain genetic backgrounds, homozygous mutants die perinatally from severe hydrocephalus, while mice on other backgrounds have an accumulation of mucus in the sinus cavity and male infertility. Mutant sperm lack mature flagella, while respiratory epithelial cilia are present but beat at a slower frequency than wild-type cilia. Transgenic rescue demonstrates that the PCD in nm1054 mutants results from the loss of a single gene encoding the novel primary ciliary dyskinesia protein 1 (Pcdp1). The Pcdp1 gene is expressed in spermatogenic cells and motile ciliated epithelial cells. Immunohistochemistry shows that Pcdp1 protein localizes to sperm flagella and the cilia of respiratory epithelial cells and brain ependymal cells in both mice and humans. This study demonstrates that Pcdp1 plays an important role in ciliary and flagellar biogenesis and motility, making the nm1054 mutant a useful model for studying the molecular genetics and pathogenesis of PCD.

Published ahead of print on 26 November 2007.

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