| RRC ID |
54531
|
| 著者 |
Yin W, Livraghi-Butrico A, Sears PR, Rogers TD, Burns KA, Grubb BR, Ostrowski LE.
|
| タイトル |
Mice with a Deletion of Rsph1 Exhibit a Low Level of Mucociliary Clearance and Develop a Primary Ciliary Dyskinesia Phenotype.
|
| ジャーナル |
Am J Respir Cell Mol Biol
|
| Abstract |
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 RSPH1 (radial spoke head 1 homolog) have been reported to have a milder phenotype than other individuals with PCD, as evidenced by a lower incidence of neonatal respiratory distress, higher nasal nitric oxide concentrations, 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 Rsph1-/-
cells appeared normal by transmission EM, whereas the remaining cilia revealed a range of defects, primarily transpositions or a missing central pair. Ciliary beat frequency in Rsph1-/-
cells was significantly lower than in control cells (20.2 ± 0.8 vs. 25.0 ± 0.9 Hz), and the cilia exhibited an aberrant rotational waveform. Young Rsph1-/-
animals demonstrated a low rate of mucociliary clearance in the nasopharynx that was reduced to zero by about 1 month of age. Rsph1-/- animals accumulated mucus in the nasal cavity but had a lower bacterial burden than animals with a deletion of dynein axonemal intermediate chain 1 (Dnaic1-/-). Thus, Rsph1-/-
mice display a PCD phenotype similar to but less severe than that observed in Dnaic1-/- mice, similar to what has been observed in humans. The results suggest that some individuals with PCD may not have a complete loss of mucociliary clearance and further suggest that early diagnosis and intervention may be important to maintain this low amount of clearance.
|
| 巻・号 |
61(3)
|
| ページ |
312-321
|
| 公開日 |
2019-9-1
|
| DOI |
10.1165/rcmb.2017-0387OC
|
| PMID |
30896965
|
| PMC |
PMC6839924
|
| MeSH |
Animals
Axoneme / genetics
Cilia / genetics
DNA-Binding Proteins / genetics*
Humans
Kartagener Syndrome / genetics*
Mice
Mucociliary Clearance / genetics*
Mutation / genetics
Phenotype*
Sequence Deletion / genetics
|
| IF |
4.34
|
| 引用数 |
1
|
| リソース情報 |
| 実験動物マウス |
RBRC02369 |
