| Item type |
文献 / Documents(1) |
| 公開日 |
2021-02-16 |
| アクセス権 |
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|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
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|
識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0240333 |
|
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言語 |
ja |
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|
関連名称 |
10.1371/journal.pone.0240333 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Fgf10-CRISPR mosaic mutants demonstrate the gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
Lung of Fgf10-CRISPR mosaic mouse |
|
言語 |
en |
| 著者 |
ハブタ, ムネノリ
泰江, 章博
スズキ, ケンイチ
フジタ, ヒロフミ
サトウ, ケイタ
コウノ, ヒトミ
タカヤマ, アユコ
バンドウ, テツヤ
ミヤイシ, サトル
親泊, 政一
田中, 栄二
大内, 淑代
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
CRISPR/Cas9-mediated gene editing often generates founder generation (F0) mice that exhibit somatic mosaicism in the targeted gene(s). It has been known that Fibroblast growth factor 10 (Fgf10)-null mice exhibit limbless and lungless phenotypes, while intermediate limb phenotypes (variable defective limbs) are observed in the Fgf10-CRISPR F0 mice. However, how the lung phenotype in the Fgf10-mosaic mutants is related to the limb phenotype and genotype has not been investigated. In this study, we examined variable lung phenotypes in the Fgf10-targeted F0 mice to determine if the lung phenotype was correlated with percentage of functional Fgf10 genotypes. Firstly, according to a previous report, Fgf10-CRISPR F0 embryos on embryonic day 16.5 (E16.5) were classified into three types: type I, no limb; type II, limb defect; and type III, normal limbs. Cartilage and bone staining showed that limb truncations were observed in the girdle, (type I), stylopodial, or zeugopodial region (type II). Deep sequencing of the Fgf10-mutant genomes revealed that the mean proportion of codons that encode putative functional FGF10 was 8.3 ± 6.2% in type I, 25.3 ± 2.7% in type II, and 54.3 ± 9.5% in type III (mean ± standard error of the mean) mutants at E16.5. Histological studies showed that almost all lung lobes were absent in type I embryos. The accessory lung lobe was often absent in type II embryos with other lobes dysplastic. All lung lobes formed in type III embryos. The number of terminal tubules was significantly lower in type I and II embryos, but unchanged in type III embryos. To identify alveolar type 2 epithelial (AECII) cells, known to be reduced in the Fgf10-heterozygous mutant, immunostaining using anti-surfactant protein C (SPC) antibody was performed: In the E18.5 lungs, the number of AECII was correlated to the percentage of functional Fgf10 genotypes. These data suggest the Fgf10 gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung. Since dysfunction of AECII cells has been implicated in the pathogenesis of parenchymal lung diseases, the Fgf10-CRISPR F0 mouse would present an ideal experimental system to explore it. |
|
言語 |
en |
| 書誌情報 |
en : PLOS ONE
巻 15,
号 10,
p. e0240333,
発行日 2020-10-15
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
19326203 |
| 出版者 |
|
|
出版者 |
PLOS |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© 2020 Habuta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
|
|
識別子 |
371858 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
pone_15_10_e0240333.pdf (4.63 MB)
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