Mice with a Deletion of Rsph1 Exhibit a Low Level of Mucociliary Clearance and Develop a PCD Phenotype

Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disease caused by mutations in over 40 different genes. Individuals with PCD caused by mutations in radial spoke head 1 homolog (RSPH1) have been reported to have a milder phenotype compared to other PCD subjects, as evidenced by a lower incidence of neonatal respiratory distress, higher nasal nitric oxide levels, and better lung function. To better understand genotype-phenotype relationships in PCD, we have characterized a mutant mouse model with a deletion of Rsph1. Approximately 50% of cilia from Rsph-/- cells appeared normal by transmission electron microscopy, while the remaining cilia revealed a range of defects, primarily transpositions or a missing central pair. Ciliary beat frequency in Rsph-/- cells was significantly lower than in controls (20.2 + 0.8 vs. 25.0 + 0.9 Hz), and the cilia exhibited an aberrant rotational waveform. Young Rsph-/- animals demonstrated a low rate of mucociliary clearance in the nasopharyn...