Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1

Lance Lee, Dean R. Campagna, Jack L. Pinkus, Howard Mulhern, Todd A Wyatt, Joseph Harold Sisson, Jacqueline A. Pavlik, Geraldine S. Pinkus, Mark D. Fleming

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)949-957
Number of pages9
JournalMolecular and cellular biology
Volume28
Issue number3
DOIs
StatePublished - Feb 1 2008

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Kartagener Syndrome
Cilia
Proteins
Male Infertility
Hydrocephalus
Epithelial Cells
Sperm Tail
Situs Inversus
Flagella
Sinusitis
Mucus
Spermatozoa
Molecular Biology
Immunohistochemistry
Phenotype
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1. / Lee, Lance; Campagna, Dean R.; Pinkus, Jack L.; Mulhern, Howard; Wyatt, Todd A; Sisson, Joseph Harold; Pavlik, Jacqueline A.; Pinkus, Geraldine S.; Fleming, Mark D.

In: Molecular and cellular biology, Vol. 28, No. 3, 01.02.2008, p. 949-957.

Research output: Contribution to journalArticle

Lee, L, Campagna, DR, Pinkus, JL, Mulhern, H, Wyatt, TA, Sisson, JH, Pavlik, JA, Pinkus, GS & Fleming, MD 2008, 'Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1', Molecular and cellular biology, vol. 28, no. 3, pp. 949-957. https://doi.org/10.1128/MCB.00354-07
Lee, Lance ; Campagna, Dean R. ; Pinkus, Jack L. ; Mulhern, Howard ; Wyatt, Todd A ; Sisson, Joseph Harold ; Pavlik, Jacqueline A. ; Pinkus, Geraldine S. ; Fleming, Mark D. / Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1. In: Molecular and cellular biology. 2008 ; Vol. 28, No. 3. pp. 949-957.
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