論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02369 |