75
Views
89
CrossRef citations to date
0
Altmetric
Article

Primary Ciliary Dyskinesia in Mice Lacking the Novel Ciliary Protein Pcdp1

, , , , , , , & show all
Pages 949-957 | Received 27 Feb 2007, Accepted 05 Nov 2007, Published online: 27 Mar 2023
 

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.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/ .

ACKNOWLEDGMENTS

This work was supported by the National Institutes of Health (HL074247 for M.D.F. and AA008769 for J.H.S.) and a Department of Veteran's Affairs Merit Review Grant (T.A.W.). L.L. was supported in part by an NIH postdoctoral NRSA training grant (HL007574.23).

We gratefully thank James Edwards and Tonora Archibald in the Children's Hospital Boston Pathology Department histology core facility, as well as Yu Yang in the Dana Farber—Partners Cancer Center in situ core facility, for their technical assistance and expertise. We thank Hannah Kinney and Robin Haynes for human brain sections. We also thank Steven Margossian for reading the manuscript, as well as Nancy Andrews and members of the Andrews and Fleming laboratories for unending discussion and suggestions.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 61.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 265.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.