Phenotypes associated with this allele
respiratory system
|
|
• while increased apoptosis of epithelial cells is rescued, mice exhibit abnormal branching morphogenesis
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mycntm1Psk mutation
(2 available);
any
Mycn mutation
(24 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
mortality/aging
|
|
• all mutants die at birth
|
respiratory system
|
|
• at E18.5 the lungs are composed of numerous large fluid-filled sacs containing cellular debris lined by highly attenuated epithelial cells separated by a thin layer of mesoderm
• however, lung size, lobulation pattern, and trachea morphology are normal
|
|
|
• at E15.5-E16.5, a reduction in the proportion of proliferating cells in the endoderm is seen (17% compared to 65% in wild-type at E15.5)
• at E15.5, E16.5 and E18.5, abundant apoptotic cells are detected in the lumen, epithelium and mesenchyme, unlike in wild-type lungs
|
|
|
• at E14.5-E16.5, branching is reduced with only a few expanded tubes separated by abundant mesoderm present
|
|
|
• at E14.5, E15.5 and E18.5, epithelial cell size is irregular, dead cells are seen in the lumen, and increased apoptosis is seen
|
|
|
• expression of Aqp5 (a marker for type I cells) is prematurely increased at E16, suggesting premature differentiation of epithelial cells
|
|
|
• at E18.5, attenuated presumptive type I cells are lining the large sacs
|
|
|
• at E18.5, a paucity of type II cells is observed in the mutant lung
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mycntm1Psk mutation
(2 available);
any
Mycn mutation
(24 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
mortality/aging
|
|
• ~50% of mutants develop normally into adulthood with no obvious lung defects
|
|
|
• ~50% of mutants die at or shortly after birth with a severe lung phenotype
|
respiratory system
|
|
• at E18.5 the lungs of affected mutants are composed of numerous large fluid-filled sacs containing cellular debris lined by highly attenuated epithelial cells separated by a thin layer of mesoderm
• however, lung size, lobulation pattern, and trachea morphology are normal
|
|
|
• at E15.5-E16.5, a reduction in the proportion of proliferating cells in the endoderm is seen
• at E15.5, E16.5 and E18.5, abundant apoptotic cells are detected in the lumen, epithelium and mesenchyme, unlike in wild-type lungs
|
|
|
• at E14.5-E16.5 in affected mutants, branching is reduced with only a few expanded tubes separated by abundant mesoderm present
|
|
|
• at E14.5, E15.5 and E18.5, epithelial cell size is irregular, dead cells are seen in the lumen, and increased apoptosis is seen
|
|
|
• at E18.5, attenuated presumptive type I cells are lining the large sacs
|
|
|
• at E18.5, a paucity of type II cells is observed in the mutant lung
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hoxa5tm1.1Ljea mutation
(0 available);
any
Hoxa5 mutation
(27 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
|
• as in mice with only Tg(Sftpc-cre)1Blh
|
|
|
• distended alveoli at the periphery of lobes at day 30 as in mice with only Tg(Sftpc-cre)1Blh
|
growth/size/body
|
|
• as in mice with only Tg(Sftpc-cre)1Blh
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hoxa5tm1.1Ljea mutation
(0 available);
any
Hoxa5 mutation
(27 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
|
• as in mice with only Tg(Sftpc-cre)1Blh
|
|
|
• distended alveoli at the periphery of lobes at day 30 as in mice with only Tg(Sftpc-cre)1Blh
|
growth/size/body
|
|
• as in mice with only Tg(Sftpc-cre)1Blh
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Juntm4Wag mutation
(0 available);
any
Jun mutation
(12 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
cellular
|
|
• mutants exhibit an increase in apoptotic cells in the lungs
|
respiratory system
|
|
• mutants exhibit an increase in apoptotic cells in the lungs
|
|
|
• mutants exhibit infiltration of atypical foamy alveolar macrophages
• mutants with prolonged exposure to cigarette smoke exhibit perivascular and peribronchiolar inflammation
|
|
|
• 3 month old mutants exhibit enlarged air spaces and infiltration of atypical foamy alveolar macrophages
• progressive destruction of alveolar tissue
|
|
|
• mutants develop progressive emphysema
|
|
|
• localized destruction leading to large cavities in the parenchyma
|
immune system
|
|
• elevated levels of IL-12p40, IL-13, and CXCL1 cytokines in the BAL
|
|
|
• an elevated level of TNF-alpha is seen in the BAL fluid
|
|
|
• mutants exhibit infiltration of atypical foamy alveolar macrophages
• mutants with prolonged exposure to cigarette smoke exhibit perivascular and peribronchiolar inflammation
|
homeostasis/metabolism
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fgf4tm1.2Mrt mutation
(1 available);
any
Fgf4 mutation
(29 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
N |
• mice exhibit normal lung morphology
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adgrf5tm1.1Bstc mutation
(1 available);
any
Adgrf5 mutation
(73 available)
Adgrf5tm1.2Bstc mutation
(0 available);
any
Adgrf5 mutation
(73 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
|
• as in Gpr116tm1.2Bstc homozygotes
|
homeostasis/metabolism
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Atp1b1tm1.1Zboro mutation
(1 available);
any
Atp1b1 mutation
(20 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
N |
• lung permeability, wet-to-dry lung weight rations and lung morphology are similar to controls
|
|
|
• 78% reduction in alveolar fluid clearance as compared to controls
|
|
|
• IEQ (equivalent short circuit current) is reduced in cultured alveolar epithelial cell monolayers as compared to controls, however, RT (transepithelial electrical resistance) is similar to controls
• cultured alveolar epithelial cell monolayers exhibit lower unidirectional Na+ flux in the apical-to-basolateral direction and unchanged Na+ flux in the basolateral-to-apical direction as compared to controls
• baseline net Na+ absorption is lower than in control monolayers
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Sor mutation
(8 available);
any
Gt(ROSA)26Sor mutation
(942 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
|
• large dilated cysts at E18.5
|
growth/size/body
|
|
• large dilated cysts at E18.5
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmp4tm3.1Blh mutation
(0 available);
any
Bmp4 mutation
(21 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
|
• at E16.5 and E18.5, 50% of mice exhibit abnormal lungs with large sacs
|
|
|
• at E16.5, cell proliferation lung epithelium and mesenchyme is decreased 50% compared to in wild-type mice while apoptosis is increased compared to in wild-type mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmpr1atm2.1Bhr mutation
(1 available);
any
Bmpr1a mutation
(89 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
N |
• Background Sensitivity: unlike on an ICR mixed background, all mice exhibit normal lung morphology
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmpr1atm2.1Bhr mutation
(1 available);
any
Bmpr1a mutation
(89 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
respiratory system
|
|
• Background Sensitivity: 46% of mice exhibit lung abnormalities between E16.5, and birth unlike when the transgene is carried on a C57BL/6 background
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmpr1atm1Bhr mutation
(1 available);
any
Bmpr1a mutation
(89 available)
Bmpr1atm2.1Bhr mutation
(1 available);
any
Bmpr1a mutation
(89 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
mortality/aging
|
|
• all mice die or are euthanized within 2 days of birth due to severe respiratory distress
|
respiratory system
|
N |
• despite defects in distal portions of the lungs, proximal bronchi and bronchioles appear normal
|
|
|
• at E16.5, the distal regions of all four lobes are abnormal
• lungs are highly abnormal with large, fluid-filled (emphysematous) sacs
• however, lungs are normal at E12.5
|
|
|
• at E16.5, the number of more distal branches is reduced and branches are smaller than in wild-type mice
• epithelial cells in the periphery of the lung have a more rounded morphology than in wild-type mice
• epithelial cells cultured in a mesenchyme-free system fail to undergo secondary branching, develop fewer or no buds and exhibit a collapsed and folded morphology compared to wild-type cultures
|
|
|
• fewer than normal as determined by surfactant C expression
|
|
|
• despite defects in distal portions of the lungs, proximal bronchi and bronchioles appear normal
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(CAG-Sox2,-EGFP)Blh mutation
(0 available);
any
Gt(ROSA)26Sor mutation
(942 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
mortality/aging
|
|
• most mice are sacrificed within a few weeks of birth with respiratory distress
|
respiratory system
|
|
• in mice surviving to 15 weeks
|
|
|
• in mice surviving to 15 weeks
|
|
|
• in mice surviving to 15 weeks
|
|
|
• in mice surviving to 15 weeks
|
|
|
• mice that survive to 15 weeks exhibit hyperplasia of the lung epithelium in the bronchi, bronchioles, and alveoli unlike wild-type mice
|
|
|
• within a few weeks of birth
|
neoplasm
|
|
• in mice surviving to 15 weeks
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fgfr2tm1Dor mutation
(3 available);
any
Fgfr2 mutation
(87 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
embryo
|
|
• E12.5 embryos are noticeably smaller than controls
|
growth/size/body
|
|
• E12.5 embryos are noticeably smaller than controls
|
respiratory system
|
|
• apoptosis is expanded caudally in the bronchial epithelium compared to controls at E11.25
• widespread apoptosis occurs in the lung epithelium by E12.5 and is also observed in the lung mesenchyme
|
|
|
• some E11.5 embryos have smaller lung branches with a bumpy, irregular
morphology
• by E12.5, irregular outgrowths have arisen along the entire length of both main bronchi of the mutant lungs with outgrowths concentrated more caudally
• mesenchymal protrusions without an accompanying epithelial branch are occasionally observed during embryonic development
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adora2btm1Msit mutation
(0 available);
any
Adora2b mutation
(19 available)
Tg(Sftpc-cre)1Blh mutation
(0 available)
|
|
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
|
|
|
respiratory system
|
|
• enlarged air spaces as early as E15.5
• dilated sacs at the periphery at P6 that may worsen with age
|
|
|
• increased apoptosis at E15.5
• 5-fold increase in apoptotic cells at E18.5
|
growth/size/body
Analysis Tools
