Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1.
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.
Lee
Lance
L
Department of Pathology, Enders 1116, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
Campagna
Dean R
DR
Pinkus
Jack L
JL
Mulhern
Howard
H
Wyatt
Todd A
TA
Sisson
Joseph H
JH
Pavlik
Jacqueline A
JA
Pinkus
Geraldine S
GS
Fleming
Mark D
MD
D000818:Animals; D001921:Brain / Q000166:cytology; D002148:Calmodulin-Binding Proteins; D002923:Cilia / Q000737:chemistry*; D004805:Ependyma / Q000737:chemistry; D004847:Epithelial Cells / Q000737:chemistry; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007619:Kartagener Syndrome / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009928:Organ Specificity; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012137:Respiratory System / Q000166:cytology; D013082:Sperm Tail / Q000737:chemistry*; D014018:Tissue Distribution
C527282:CFAP221 protein, human; D002148:Calmodulin-Binding Proteins; C527281:Pcdp1 protein, mouse; D011506:Proteins