Analysis Tools|
Allele Symbol Allele Name Allele ID |
Nedd4ltm1.1Hkb targeted mutation 1.1, Hiroshi Kawabe MGI:4940977 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice induced with doxycycline show neither an amelioration nor aggravation of the lung disease phenotype that is seen in conditional Nedd4l knock-out mice
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• lungs from doxycycline treated mice show hallmarks of interstitial pulmonary fibrosis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit an overall mortality of 70% at 4 months on doxycycline
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• mice induced with doxycycline exhibit mortality associated with severe weight loss and hypoxia after approximately 3 months on doxycycline, resulting in an overall mortality of 70% at 4 months on doxycycline
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• mice show severe weight loss after approximately 3 months on doxycycline
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• bronchoalveolar lavage fluid shows activated macrophages and total cells, macrophages, neutrophils, and cytokines such as interleukin-1beta, keratinocyte-derived chemokine, and interleukin-13 are increased from 2-3 months on doxycycline
• inflammatory markers including neutrophils, and levels of IL-13 and IL-1beta in bronchoalveolar lavage fluid are reduced in lungs of pirfenidone-treated mice
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• lungs from doxycycline treated mice show traction bronchiectasis
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• lungs of doxycycline induced mice exhibit epithelial remodeling of the peripheral airways characterized by a decrease in club cells and increase in ciliated cells and goblet cells in distal and terminal airways and increase in production of Muc5b in epithelial cells along the tracheobronchial tree extending into terminal airways and in honeycomb-like cysts
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• lungs from doxycycline treated mice show hypertrophy of alveolar type 2 cells
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• lungs from doxycycline treated mice show hallmarks of interstitial pulmonary fibrosis, including reticular opacities, traction bronchiectasis, and honeycombing-like cysts with spatially heterogenous distribution in peripheral regions of the lung
• lungs from doxycycline treated mice show areas of patchy fibrosis of the alveolar interstitium associated with inflammatory infiltrates, alpha smooth muscle actin-positive fibroblast foci-like structures, increased collagen deposition, septal wall thickening, hypertrophy of alveolar type 2 cells, subpleural microscopic honeycombing-like cysts, and Muc5b-positive material within fibrotic areas of peripheral airspaces
• mice treated with pirfenidone for 4 weeks two months after tamoxifen induction, when lungs show first signs of fibrotic remodeling, exhibit reduced fibrosis
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• increase in ENaC activity is associated with reduced airway surface liquid height and reduced mucociliary transport velocity on primary airway cultures
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• pulmonary function testing shows progressive restriction with a 45% decrease in static compliance at 4 months on doxycycline
• mice treated with pirfenidone for 4 weeks two months after tamoxifen induction show improved static compliance
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• transepithelial bioelectric measurements preformed after 2 weeks of doxycycline induction show an approximately 3-fold increase in amiloride-sensitive epithelial Na+ channel (ENaC)-mediated Na+ currents in freshly excised airway tissues
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• bronchoalveolar lavage fluid shows activated macrophages and total cells, macrophages, neutrophils, and cytokines such as interleukin-1beta, keratinocyte-derived chemokine, and interleukin-13 are increased from 2-3 months on doxycycline
• inflammatory markers including neutrophils, and levels of IL-13 and IL-1beta in bronchoalveolar lavage fluid are reduced in lungs of pirfenidone-treated mice
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• lungs from doxycycline treated mice show traction bronchiectasis
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• lungs of doxycycline treated mice show elevated levels of active TGFbeta
• mice treated with pirfenidone for 4 weeks two months after tamoxifen induction show decreased concentrations of active TGFbeta in lungs
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| idiopathic pulmonary fibrosis | DOID:0050156 | J:292026 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die between 2 and 3 weeks of age likely from airway obstruction and asphyxiation
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• mice exhibit large dense patches consisting of infiltrating neutrophils that is not secondary to bacterial infection unlike control mice
• however, treatment with amiloride reduces inflammation
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• mice exhibit decreased lung wet/dry ratio compared with control mice
• however, treatment with amiloride improves lung defects
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• mice exhibit cystic fibrosis-like defects unlike control mice
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• mice exhibit increased nonciliated mucus secreting (mostly goblet) cells in the trachea unlike control mice
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• mice exhibit increased nonciliated mucus secreting (mostly goblet) cells in the trachea unlike control mice
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• airway periciliary liquid layer in the trachea is decreased in height compared to in control mice
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• mice exhibit large dense patches consisting of infiltrating neutrophils that is not secondary to bacterial infection unlike control mice
• however, treatment with amiloride reduces inflammation
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 07/14/2026 MGI 6.24 |
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