|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• newborn mice exposed to doxycycline from E14.5 to birth display defective distal lung saccular development due to reduced primary septation
|
|
• newborn mice exposed to doxycycline from E14.5 to birth display dilated distal airspaces with only few primary septae, unlike wild-type controls where extensive numbers of saccules are observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with doxycycline from E0.5 display normal postnatal survival and normal lung morphology with no detectable changes in the cellular differentiation or development of peripheral lung epithelium at all stages analyzed (E12.5 to adulthood)
|
| N |
• mice treated with doxycycline from E0.5 display normal survival and repair after hyperoxia-induced lung injury (95% oxygen for 3 days) relative to control littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• under normoxic conditions, mice treated with doxycycline from E0 to P25 exhibit no differences in survival at E18.5 or after birth relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display increased IL-1beta, IL-6, and MIP-2 levels in lung tissue relative to control littermates
|
|
• when doxycycline is administered from E0 to P25, adult mice are more susceptible to hyperoxia-induced (95% O2 for 65 hrs) lung injury than oxygen-exposed control littermates, displaying an earlier onset of respiratory symptoms, significantly reduced survival, and severe lung injury as shown by hemorrhage, perivascular and lymphatic edema, loss of bronchiolar and alveolar epithelia, severe epithelial cell necrosis, thickened alveoli, extensive inflammation and frequent airspace enlargement
• intratracheal treatment with exogenous surfactant protein B improves survival and lung histology in doxycycline-treated mice 4 days after hyperoxia exposure
|
| N |
• under normoxic conditions, mice treated with doxycycline from E0 to P25 exhibit normal lung size and morphology and normal pulmonary mechanics relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display loss of alveolar capillary membrane integrity, perivascular edema, and severe vascular cell necrosis relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display widespread alveolar epithelial cell necrosis without apoptosis
• after exposure to hyperoxia, doxycycline-treated mice display extensive epithelial cell necrosis in the bronchiolar epithelium
|
|
• after exposure to hyperoxia, doxycycline-treated mice display increased infiltration by polymorphonuclear cells and alveolar macrophages along with an increased production of IL-1beta, IL-6, and MIP-2 relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display widespread alveolar epithelial cell necrosis without apoptosis, hyaline membrane formation, loss of alveolar capillary membrane integrity, and increased inflammation consistent with severe epithelial cell injury
|
|
• after exposure to hyperoxia, staining for proSP-C, a selective marker for type II cells, is decreased in doxycycline-treated mice
|
|
• after exposure to hyperoxia, doxycycline-treated mice display hyaline membrane formation
|
|
• after exposure to hyperoxia, doxycycline-treated mice display significantly increased lung elastance
|
|
• after exposure to hyperoxia, doxycycline-treated mice display significantly increased tissue damping
|
|
• doxycycline-treated mice develop acute respiratory distress within 72 hrs of hyperoxia, unlike control littermates which develop severe respiratory symptoms after 5 or more days of continued exposure
|
|
• after exposure to hyperoxia, doxycycline-treated mice display altered pulmonary mechanics, indicating a decline in pulmonary function
• however, hysteresivity and newtonian resistance remain unaffected
|
|
• after exposure to hyperoxia, doxycycline-treated mice display a significant increase in airway resistance relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display reduced lung compliance relative to control littermates
|
|
• doxycycline-treated mice exhibit respiratory failure after relatively short periods of hyperoxia
|
|
• after exposure to hyperoxia, doxycycline-treated mice show significantly increased BALF protein content and reduced alveolar surfactant phospholipid (saturated phosphatidylcholine) pool sizes relative to control littermates
• after exposure to hyperoxia, SP-B is undetectable while SP-A is significantly decreased in alveolar lavage of doxycycline-treated mice
|
|
• after exposure to hyperoxia, doxycycline-treated mice display increased IL-1beta, IL-6, and MIP-2 levels in lung tissue relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display increased infiltration by polymorphonuclear cells and alveolar macrophages along with an increased production of IL-1beta, IL-6, and MIP-2 relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display loss of alveolar capillary membrane integrity, perivascular edema, and severe vascular cell necrosis relative to control littermates
|
|
• after exposure to hyperoxia, doxycycline-treated mice display widespread alveolar epithelial cell necrosis without apoptosis
• after exposure to hyperoxia, doxycycline-treated mice display extensive epithelial cell necrosis in the bronchiolar epithelium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice treated with doxycycline from E0 die on P1
|
|
• 50% of mice treated with doxycycline from E0 through P16 died within 30 days of birth
(J:88601)
• only 46% of mice treated with doxycycline from E0 survive to P5
(J:93473)
|
|
• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
|
|
• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
|
|
• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
|
|
• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
|
|
• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion
|
|
• impaired alveogenesis marked by fewer peripheral lung saccules and decreased alveolar septation; apparent at 3 days of age in mice treated with doxycycline from E0 through P16
(J:88601)
|
|
• at E18.5, mice treated with doxycycline from E0 display immature peripheral lung saccules, resembling those normally seen at E16-E17
|
|
• at E18.5, squamous type I cells are missing, alveolar walls are thickened and lined by immature cuboidal type II cells, cytoplasmic glycogen is dispersed, and apical microvilli are absent
• however, no evidence of capillary leakage or endothelial cell abnormalities are observed
|
|
• at E18.5, no squamous type I cells are observed in mice treated with doxycycline from E0
|
|
• at E18.5, mice treated with doxycycline from E0 show absence of lamellar bodies in alveolar type II cells
|
|
• at E18.5, mice treated with doxycycline from E0 show thickened alveolar walls lined by immature cuboidal type II cells
|
|
• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display focal or extensive atelectasis
|
|
• increased airspace in mice prenatally treated with doxycycline
• postnatal treatment with doxycycline also resulted in increased airspace but to a lesser extent
• normal prenatal lung morphogenesis
|
|
• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display hyaline membrane formation
|
|
• goblet cell hyperplasia, associated with the accumulation of both neutral and acidic mucins, observed in mice treated with doxycycline from E0 through P16
|
|
• ~50% of mice treated with doxycycline from E0 develop severe respiratory distress within 2-3 hrs of birth
|
|
• at E18.5, the fractional content of phosphatidylcholine (PC) and saturated PC are markdely reduced, whereas that of phosphatidylethanolamine, sphingomyelin, and phosphatidylserine is increased in the lungs of mice treated with doxycycline from E0
|
|
• SP-A, SP-B, and SP-C mRNAs are significantly decreased at E18.5
• the active SP-B peptide is markedly decreased in lung homogenates prior to birth
• SP-D mRNAs are significantly increased at E18.5
|
|
• at E18.5, no secreted surfactant is detected in the air spaces of mice treated with doxycycline from E0
|
 |
• newborn mice are frequently cannibalized by the mother
|
|
• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ~10% of mice treated with doxycycline in utero (E10-E16) survive to adulthood but develop spontaneous lung tumors, not observed in wild-type controls during a 90-wk observation period
• the cancer-free survival rates for prenatally doxycycline-treated mice are significantly lower than for controls
|
|
• ~90% of mice treated with doxycycline in utero (E10-E16) die within 2 hrs of birth due to respiratory failure
• in contrast, mice treated with doxycycline postnatally (P21-P27 or P84-P90) do not show any neonatal lethality
|
|
• neonates treated with doxycycline in utero (E10-E16) display a cyanotic skin color
|
|
• neonates treated with doxycycline in utero (E10-E16) display significant hypoxia
|
|
• neonates treated with doxycycline in utero (E10-E16) display respiratory acidosis
|
|
• following urethane treatment, 94% (17 of 18) of mice treated with doxycycline in utero (E10-E16) developed lung tumors (one lung adenocarcinoma, the rest being lung adenomas) relative to only 42% (11 of 26) of wild-type controls (all lung adenomas); also seen in mice treated with doxycycline postnatally (P21-P27)
• both prenatal and postnatal doxycycline treatment resulted in significantly increased numbers and sizes of urethane-induced lung tumors relative to those seen in wild-type controls
|
|
• at birth, mice treated with doxycycline in utero (E10-E16) show a 1.5-fold increase in total lung cell numbers relative to controls
• at E19.5, the numbers of both alveolar epithelial cells and mesenchymal cells are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
|
|
• neonates treated with doxycycline in utero (E10-E16) display respiratory acidosis
|
|
• 13 of 14 mice treated with doxycycline in utero (E10-E16) developed lung adenocarcinomas, not observed in any wild-type controls during a 90-wk observation period
• 13 of 15 (87%) of mice treated with doxycycline postnatally (P21-P27) developed spontaneous lung adenocarcinomas, not observed in any wild-type controls during the 40- to 70-wk observation period
• notably, Kras was mutated in 33% of spontaneous lung adenocarcinomas observed in P21-P27 doxycycline treated mice
|
|
• 1 of 14 mice treated with doxycycline in utero (E10-E16) developed a lung squamous cell carcinoma
|
|
• mice treated with doxycycline in utero (E10-E16) display delayed lung development at the terminal sac stage (E17.5 to P0) relative to control mice
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) show an expanded mesenchymal cell population, due to increased numbers of myofibroblast precursors in the septa
• mesenchymal cell numbers are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
|
|
• at the terminal sac stage (E17.5 to P0), mice treated with doxycycline in utero (E10-E16) display fewer saccular structures with a significant delay in the dilatation of the distal tubules relative to control mice
• at birth, mice treated with doxycycline in utero (E10-E16) display septal hyperplasia with increased mesenchymal cells and reduced airspaces relative to controls
|
|
• at birth, mice treated with doxycycline in utero (E10-E16) display reduced airspaces relative to controls
|
|
• at 8 weeks of age, mice treated with doxycycline postnatally (P21-P27) show a 5.2-fold increase in BASCs and a 4.0-fold increase in side population cells relative to wild-type controls; similar increases are observed in E10-E16 doxycycline treated mice
|
|
• neonates treated with doxycycline in utero (E10-E16) display significant bronchiolar epithelial hyperplasia relative to controls
• mice treated with doxycycline postnatally (P21-P27 or P84-P90) display mild bronchiolar epithelial hyperplasia relative to controls; however no significant differences in bronchiolar epithelial differentiation are observed
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) display increased numbers of undifferentiated cuboidal alveolar epithelial cells of enlarged size relative to controls
• mice treated with doxycycline postnatally (P21-P27 or P84-P90) display mild alveolar epithelial hyperplasia and increased cell size of alveolar epithelial cells relative to controls; however, no significant differences in alveolar epithelial differentiation are observed
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) display impaired type I cell differentiation, as shown by severely reduced aquaporin-5 (AQP5) immunostaining relative to controls
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) display immature rounded to cuboidal cells with poorly differentiated cytoplasm, rare apical microvilli, few lamellar bodies, and severely reduced SP-C immunostaining relative to control mice
• at P0, mice treated with doxycycline in utero (E10-E16) also display PAS positivity unlike wild-type control mice
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) display fewer lamellar bodies than control mice
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) display a much thicker blood-air barrier than control mice
|
|
• neonates treated with doxycycline in utero (E10-E16) display irregular breathing and gasping
|
|
• ~90% of mice treated with doxycycline in utero (E10-E16) die of respiratory failure
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) display a significant reduction in the expression levels of surfactant proteins A (SP-A), SP-B, SP-C and SP-D relative to control mice
|
|
• following urethane treatment, 94% (17 of 18) of mice treated with doxycycline in utero (E10-E16) developed lung tumors (one lung adenocarcinoma, the rest being lung adenomas) relative to only 42% (11 of 26) of wild-type controls (all lung adenomas); also seen in mice treated with doxycycline postnatally (P21-P27)
• both prenatal and postnatal doxycycline treatment resulted in significantly increased numbers and sizes of urethane-induced lung tumors relative to those seen in wild-type controls
|
|
• 13 of 14 mice treated with doxycycline in utero (E10-E16) developed lung adenocarcinomas, not observed in any wild-type controls during a 90-wk observation period
• 13 of 15 (87%) of mice treated with doxycycline postnatally (P21-P27) developed spontaneous lung adenocarcinomas, not observed in any wild-type controls during the 40- to 70-wk observation period
• notably, Kras was mutated in 33% of spontaneous lung adenocarcinomas observed in P21-P27 doxycycline treated mice
|
|
• 1 of 14 mice treated with doxycycline in utero (E10-E16) developed a lung squamous cell carcinoma
|
|
• at E19.5, mice treated with doxycycline in utero (E10-E16) show an expanded mesenchymal cell population, due to increased numbers of myofibroblast precursors in the septa
• mesenchymal cell numbers are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
|
|
• at birth, mice treated with doxycycline in utero (E10-E16) show a 1.5-fold increase in total lung cell numbers relative to controls
• at E19.5, the numbers of both alveolar epithelial cells and mesenchymal cells are significantly increased due to enhanced cell proliferation rather than reduced apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die within an hour of birth when exposed to doxycycline 8 days prior to parturition
• 85% of mice die within an hour of birth when exposed to doxycycline 4 of 6 days prior to parturition
|
|
• at birth when mice are exposed to doxycycline prior to parturition
|
|
• when mice are exposed to doxycycline prior to parturition, mice exhibit reduced alveolar airspaces unlike wild-type mice
|
|
• when mice are exposed to doxycycline prior to parturition, the alveolar surface is lined with immature pneumocytes unlike in wild-type mice
|
|
• when mice are exposed to doxycycline prior to parturition, the alveolar septa has only a few scattered type II cells unlike in wild-type mice
|
|
• at birth when mice are exposed to doxycycline prior to parturition
|
|
• at birth when mice are exposed to doxycycline prior to parturition
|
|
• at birth when mice are exposed to doxycycline prior to parturition
|
|
• when mice are exposed to doxycycline prior to parturition
|
|
• at birth when mice are exposed to doxycycline prior to parturition
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal airway epithelium morphology and no evidence of inflammation
|
|
• methacholine-treated mice exhibit increased narrowing in airways compared with control mice
• lung slices treated with methacholine in vitro exhibit increased narrowing compared with control slices
• spermine has no increase in contraction unlike in control samples
• however, putrescine has no effect on airway contraction
|
|
• excised tracheal rings (with or without epithelium) treated with methacholine exhibit increased in vitro force generation compared with control rings
• lung slices and tracheal rings exhibit increased contractile response to 5-HT compared with control samples
|
|
• in response to acetylcholine
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with doxycycline at 1 month of age for 3 days then injected with cardiotoxin into the quadriceps muscle to induce inflammation and muscle damage develop large heterotopic ossification tissue masses
• treatment of cardiotoxin-induced muscle injury with palovarotene diminishes heterotopic ossification formation by more than 80%
|
|
• about 14 days after heterotopic ossification induction by injury in doxycycline treated mice, movement of affected legs is impaired
• treatment with palovarotene of mice with cardiotoxin-induced muscle injury rescues the impaired movement
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycyline treated mice exhibit an increase in proliferation of epithelial cells lining conducting airways
|
|
• papillary epithelial hyperplasia is seen as early as 4-6 weeks of age in mice treated with doxycycline
• papillary epithelial hyperplasia is characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protrude into the airway lumens
|
|
• doxycyline treated mice exhibit an increase in proliferation of nonciliated bronchial and bronchiolar Clara cells
|
|
• mice treated with doxycycline exhibit bronchiolar epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells
|
|
• mice treated with doxycycline exhibit bronchial epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells
|
|
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity
|
|
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity
|
| N |
• overt pulmonary tumors are not observed in doxycycline treated mice at 6 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline (dox) treated mice rapidly develop invasive urothelial cancer
• tumors of dox treated mice are high-grade urothelial carcinomas, grow mostly with a solid, non-glandular pattern and show blunt cellular atypia and focal glandular differentiation
• tumors invade the lamina and muscularis propria
• marker analysis indicates that tumors are related to human basal BLCA3 subtype
|
|
• doxycycline (dox) treated mice rapidly develop invasive urothelial cancer
• tumors of dox treated mice are high-grade urothelial carcinomas, grow mostly with a solid, non-glandular pattern and show blunt cellular atypia and focal glandular differentiation
• tumors invade the lamina and muscularis propria
• marker analysis indicates that tumors are related to human basal BLCA3 subtype
|
|
• 12 of 18 mice develop unilateral or bilateral hydronephrosis as early as 2 weeks after dox treatment due to obstruction of the upper ureter by tumor masses
|
|
• due to bladder tumors in dox treated mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:227748 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• although born in Mendelian ratios, most mice exposed to doxycycline from conception die of respiratory failure at birth
|
|
• doxycycline-exposed newborn mice show a reduction of airspace, sometimes obliterating the alveolar structure
|
|
• in addition, neonatal alveolar cells show significantly decreased numbers of TUNEL-positive cells, indicating reduced apoptosis
• doxycycline-exposed newborn mice display increased numbers of Ki-67-positive alveolar cells, indicating increased alveolar cell proliferation
|
|
• doxycycline-exposed newborn mice lack type I alveolar cells
|
|
• alveoli of doxycycline-exposed newborn mice are lined by immature cuboidal type II cells with a clear cytosol, round nuclei and high glycogen content, indicating a type II cell differentiation arrest
|
|
• immature type II alveolar cells of doxycycline-exposed newborn mice lack lamellar bodies
|
|
• doxycycline-exposed newborn mice lack mature type II alveolar cells
|
|
• doxycycline-exposed newborn mice display thicker alveolar walls due to marked cellular accumulation
|
|
• 86% of mice exposed to doxycycline from conception show signs of respiratory distress within hours after birth
|
|
• most mice exposed to doxycycline from conception to birth display respiratory failure
|
|
• doxycycline-exposed newborn mice show a marked loss of surfactant protein B (SP-B) by immunostaining
• mRNAs for SP-A and SP-D are significantly down-regulated
|
| N |
• doxycycline-exposed mice have a normal liver architecture and show normal Cebpa mRNA levels in liver
|
| N |
• doxycycline-exposed mice exhibit normal granulocytic differentiation in fetal liver and contain granulocytes in peripheral blood
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the 24 hour fasting-induced increase in plasma uridine that is seen in wild-type mice is reduced in doxycycline (Dox)-treated mutant mice
• however, mice do not show a reduced lipolysis response to the Beta3 adrenergic receptor agonist CL316,243
|
|
• mice that are switched to a Dox high-fat diet at 69 weeks of age show a higher fat mass than controls 4 weeks after the diet switch
• however, Dox-treated mice fed a high-fat diet do not show a difference in body weight gain from wild-type mice fed the same diet
|
|
• mice that are switched to a Dox high-fat diet at 69 weeks of age show a higher fat mass than controls 4 weeks after the diet switch
• however, Dox-treated mice fed a high-fat diet do not show a difference in body weight gain from wild-type mice fed the same diet
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants on a doxycycline diet exhibit craniofacial malformations
|
|
• 35% of mutants on a doxycycline diet for at least 3 weeks starting at P25 die during the 12 weeks following doxycycline administration; males and females die at similar rates
|
|
• 24% of the remaining surviving mutants on a doxycycline diet for at least 3 weeks starting at P25 exhibit tumors within the bladder lumen; 11 mutants have single tumor and 18 have multifoci tumors
• tumors in doxycline fed mutants resemble low-grade papillary urothelial carcinoma, exhibit polypoid structure, and the urothelium has lost its typical polarity and shows nuclear atypia, high mitogenic activity, and vascular infiltration
• however, no nuclear pleomorphism or muscle invasion is seen
• 45% of males on the doxycycline diet develop bladder tumors compared to 3% of females on the diet
• only 12.5% of castrated males after 3 months of doxycycline treatment develop luminal tumors and cell proliferation is 20% less than in noncastrated males
|
|
• urothelia of males on the doxycycline diet is more severely affected than in females
• increase in urothelial basal cell proliferation is seen in mutants fed doxycycline
• bladders of males 5 weeks after doxycline treatment show a higher proliferation index than females at the same stage
|
|
• 24% of the remaining surviving mutants on a doxycycline diet for at least 3 weeks starting at P25 exhibit tumors within the bladder lumen; 11 mutants have single tumor and 18 have multifoci tumors
• tumors in doxycline fed mutants resemble low-grade papillary urothelial carcinoma, exhibit polypoid structure, and the urothelium has lost its typical polarity and shows nuclear atypia, high mitogenic activity, and vascular infiltration
• however, no nuclear pleomorphism or muscle invasion is seen
• 45% of males on the doxycycline diet develop bladder tumors compared to 3% of females on the diet
• only 12.5% of castrated males after 3 months of doxycycline treatment develop luminal tumors and cell proliferation is 20% less than in noncastrated males
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:202618 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 die within the first 24 hrs after birth due to respiratory failure
|
| N |
• mice treated with doxycycline during postnatal period P3-P30 show no differences in overall lung morphology or expression of epithelial marker proteins relative to control littermates
|
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display pulmonary congestion
|
|
• mice treated with doxycycline from E7.5 to E14.5 display delayed lung maturation, as shown by reduced lung sacculation and mesenchymal thickening prior to birth (E17.5 and E18.5)
• however, branching morphogenesis and proliferation of distal respiratory epithelial cells is normal at E15.5 and E18.5
• no vascular abnormalities are detected at E18.5, as shown by normal Pecam-1 staining
• differentiation of ciliated and Clara cells in conducting airways remains normal
|
|
• mice treated with doxycycline from E7.5 to E14.5 display reduced lung sacculation prior to birth
• consistent with delayed lung maturation, peripheral lung tubules remain closed, unlike in control littermates
|
|
• mice treated with doxycycline from E7.5 to E14.5 display smaller peripheral saccules at E17.5 and E18.5
|
|
• increased mesenchymal thickness prior to birth
|
|
• mice treated with doxycycline from E7.5 to E14.5 show delayed differentiation of type I and type II epithelial cells
|
|
• mice treated with doxycycline from E7.5 to E14.5 display reduced numbers of squamous type I epithelial cells
• however, type I epithelial cells appear ultrastructurally normal
|
|
• mice treated with doxycycline from E7.5 to E14.5 show significantly smaller lamellar bodies in type II cells relative to control littermates
|
|
• mice treated with doxycycline from E7.5 to E14.5 display focal atelectasis
|
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display pulmonary congestion, focal atelectasis, bronchial occlusion, and hyaline membranes lining terminal airways consistent with severe respiratory distress syndrome (RDS)
• ~18% of mice treated with doxycycline from E7.5 to E14.5 survive after birth and exhibit mild RDS with focal atelectasis
|
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display hyaline membranes lining the terminal airways
|
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display severe respiratory distress
|
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 die within the first 24 hrs after birth due to respiratory failure
|
|
• mice treated with doxycycline from E7.5 to E14.5 show reduced pulmonary SP-A, SP-B, SP-C, and SP-D mRNA levels at E17.5 relative to control littermates
• SP-B mRNA is reduced to 40% of control values
|
|
• 82% of mice treated with doxycycline from E7.5 to E14.5 display pulmonary congestion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands
|
|
• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands
|
|
• mutants treated with doxycycline from P1 to P16 exhibit loss of conjunctival goblet cells
|
|
• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands
|
|
• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands
|
|
• mutants treated with doxycycline from P1 to P16 show degeneration of ocular glands, including lacrimal and Meibomian glands
|
|
• mutants treated with doxycycline from P1 to P16 show hair loss on the skin and eyelids
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die within 2 to 3 hours of birth
|
|
• capillary beds in lungs are immature
• however, vascular smooth muscle development is normal
|
|
• at birth, mice exhibit pulmonary congestion
|
|
• between E16.5 and E18.5, mice exhibit reduced dilation of the saccules, thick mesenchyme and a lack of squamous type I cells unlike in wild-type mice
|
|
• type I cell maturation is disrupted
|
|
• mature type I cells are absent
|
|
• type II cell maturation is disrupted and cells lack stored pulmonary surfactant
|
|
• at birth
|
|
• at birth
|
|
• mice produce less surfactant protein than wild-type mice
|
|
• capillary beds in lungs are immature
• however, vascular smooth muscle development is normal
|
|
• at birth, mice exhibit pulmonary congestion
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered doxycycline (Dox) exhibit an increase in IFN-gamma production in the lungs
|
|
• mice treated with Dox show pulmonary inflammation, with infiltration of mononuclear cells in the alveolar wall and general interstitium, indicating interstitial pneumonia
• however, mice treated with Dox do not exhibit emphysema, swelled alveolar macrophages, hyaline membranes, or proteinaceous debris, and show no evidence of increased lung volumes or cardiomegaly
|
|
• mice treated with Dox show pulmonary inflammation, with infiltration of mononuclear cells in the alveolar wall and general interstitium, indicating interstitial pneumonia
• however, mice treated with Dox do not exhibit emphysema, swelled alveolar macrophages, hyaline membranes, or proteinaceous debris, and show no evidence of increased lung volumes or cardiomegaly
|
|
• mean alveolar chord length is lower than in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline treated mice die shortly after birth due to respiratory distress
|
|
• in doxycycline treated mice, pulmonary mesenchyme is thickened and blood vessels are not found in close proximity to epithelial cells unlike in wild-type mice
• in doxycycline treated mice, lung maturation during saccule development is inhibited
• however, at E15.5 lung development is normal
|
|
• at birth, doxycycline treated mice exhibit hypercellular alveolar saccules without the dilated peripheral saccules found in wild-type mice
• saccules in doxycycline treated mice are thickened compared to in wild-type mice
|
|
• doxycycline treated mice exhibit thickened lung mesenchyme
|
|
• at birth, doxycycline treated mice exhibit a decrease in alveolar luminal area compared to wild-type mice
|
|
• at birth, doxycycline treated mice exhibit a decrease in squamous epithelial cells compared to in wild-type mice indicating a lack of alveolar type I cell differentiation
• however, pulmonary epithelial cell proliferation following dooxycycline treatment is normal
|
|
• at birth, doxycycline treated mice exhibit a decrease in squamous epithelial cells compared to in wild-type mice
|
|
• in doxycycline treated mice, type II cells lack lamellar structures found in wild-type cells
|
|
• doxycycline treated mice die shortly after birth due to respiratory distress
|
|
• unlike in wild-type mice, no surfactant secretion or Sftpb protein is detected in doxycycline treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Itga3tm1Hap/Itga3tm1Hap Tg(SFTPC-rtTA)5Jaw/? Tg(tetO-cre)1Jaw/? mice exhibit increased bronchoalveolar lavage cellularity at baseline and after bleomycin injury
|
• cellularity in BAL fluid is almost double that of controls in mice with cre induction
• increase in cellularity is also found after bleomycin injury of the lung
|
|
• there is about a 2-fold increase in the number of type II alveolar cells present in the lungs of mice treated with doxycycline
|
|
• alveolar septa are thickened with increased deposition of collagen IV in mice with cre induction
|
|
• bleomycin injury of the lungs leads to less fibrosis three weeks later due to impaired myofibroblast accumulation and reduced type I collagen response
• the number of myofibroblast per field is 4-5 fold less than in controls after bleomycin injury
|
|
• there is a trend towards less compliance in these mice after bleomycin injury than in controls
|
|
• cellularity in BAL fluid is almost double that of controls in mice with cre induction
• increase in cellularity is also found after bleomycin injury of the lung
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• epithelial to mesenchymal transition results from bleomycin-mediated injury of the lung
• only 1.4% of GFP+, epithelium derived cells express mesenchyme markers 17 days after bleomycin injury compared to 7.0% in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice die shortly after birth
|
|
• at E18.5, myofibroblasts in the lungs of doxycycline-treated mice exhibit reduced differentiation, as determined by sma+ expression, compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• newborn mice exposed to doxycycline from E6.5 develop respiratory distress and die within 1-2 hrs of birth
|
|
• at E18.5, doxycycline-exposed mice display an almost complete absence of pulmonary capillaries associated with defective primary septation during distal lung morphogenesis
• at E18.5, lung saccular walls without capillaries exhibit no septae while septae containing a residual (single) capillary or disorganized capillaries are malformed and show abnormal shapes with an expanded mesenchyme
|
|
• at E18.5, doxycycline-exposed mice exhibit significantly reduced pulmonary endothelial cell development relative to controls
|
|
• at birth, doxycycline-exposed mice display white lungs, indicating a lack of pulmonary circulation
|
|
• mice exposed to doxycycline from E6.5 display defective distal lung saccular development due to reduced primary septation; first seen at E16.5 when terminal tubules appear more dilated
• defective distal airspace morphogenesis is also noted when mice are exposed to doxycycline from E14.5 to birth
• impaired primary septation is likely due to reduced hepatocyte growth factor (Hgf) expression
|
|
• at E18.5, doxycycline-exposed mice display a significant reduction in proliferating (BrdU+) lung mesenchymal cells relative to controls
|
|
• at E18.5, doxycycline-exposed mice display significantly dilated distal airspaces with fewer subdivisions by primary septae than controls
• at E18.5, doxycycline-exposed mice display a mosaic pattern of normal and abnormal septae that is dependent on the residual capillary structures
• at birth, ventilation of doxycycline-exposed lungs results in marked dilation of terminal airspaces and thinning of saccular walls
|
|
• at E18.5, doxycycline-exposed mice display a 65% reduction in proliferating (BrdU+) lung epithelial cells relative to controls
• however, epithelial cell survival and proximal-distal patterning of epithelial cell differentiation remain normal
|
|
• at E16.5 and E17.5, doxycycline-exposed mice display abnormal distal acini and more dilated distal tubules than controls
|
|
• newborn mice exposed to doxycycline from E6.5 develop respiratory distress and die within 1-2 hrs of birth
|
|
• at E18.5, doxycycline-exposed mice display an almost complete absence of pulmonary capillaries associated with defective primary septation during distal lung morphogenesis
• at E18.5, lung saccular walls without capillaries exhibit no septae while septae containing a residual (single) capillary or disorganized capillaries are malformed and show abnormal shapes with an expanded mesenchyme
|
|
• at E18.5, doxycycline-exposed mice exhibit significantly reduced pulmonary endothelial cell development relative to controls
|
|
• at E18.5, doxycycline-exposed mice display significantly reduced pulmonary capillary angiogenesis associated with defective primary septation during distal lung morphogenesis
|
|
• at birth, doxycycline-exposed mice display white lungs, indicating a lack of pulmonary circulation
|
|
• at E18.5, doxycycline-exposed mice display a significant reduction in proliferating (BrdU+) lung mesenchymal cells relative to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E18.5, doxycycline-exposed mice exhibit a reduction in pulmonary endothelial cell development that is intermediate between those of wild-type controls and those carrying two Vegfatm2Gne alleles
|
|
• newborn mice exposed to doxycycline from E6.5 display pale lungs, indicating reduced pulmonary circulation
|
|
• mice exposed to doxycycline from E6.5 display defective distal lung saccular development due to moderately reduced primary septation
|
|
• at E18.5, doxycycline-exposed mice display dilated distal airspaces of a size that is intermediate between those of wild-type controls and those carrying two Vegfatm2Gne alleles
• the mean linear intercept, a reflection of airspace size and hence an indirect measure of septation incidence, is inversely related to the Vegfa gene dosage
|
|
• at E18.5, doxycycline-exposed mice exhibit a reduction in pulmonary endothelial cell development that is intermediate between those of wild-type controls and those carrying two Vegfatm2Gne alleles
|
|
• newborn mice exposed to doxycycline from E6.5 display pale lungs, indicating reduced pulmonary circulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced pulmonary inflammation in mice treated with doxycycline and intranasal rIL17
|
|
• reduced pulmonary inflammation in mice treated with doxycycline and intranasal rIL17
|
|
• reduced pulmonary inflammation in mice treated with doxycycline and intranasal rIL17
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after doxycycline treatment
|
|
• in the long bones after doxycycline treatment
|
|
• proximal tibial trabecular bone volume/total volume is increased 6.6 fold at 2 months of age after doxycycline treatment
|
|
• markedly increased after doxycycline treatment
|
|
• marked increase in the trabecular bone mass in both primary and secondary ossification centers
|
|
• increased bone formation after doxycycline treatment
|
|
• after doxycycline treatment
|
|
• after doxycycline treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice show increased susceptibility to influenza A virus infection, showing increased influenza A replication
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice show increased susceptibility to pseudorabies
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show a moderate size reduction of adipocytes in subcutaneous white adipose tissue (sWAT) when fed a Dox-containing diet
• however, no differences in epididymal white adipose tissue (eWAT) or interscapular brown adipose tissue (BAT) adipocyte size is seen
|
| N |
• mice do not show differences in bodyweight gain from wild-type mice when treated with doxycycline (Dox)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with Dox at P28 for 2 weeks and analyzed at 41-42 weeks of age show slow development of kidney cysts
• mice treated with Dox at P0 and analyzed at P14 show a modest kidney phenotype, with a few cysts
• however, blood urea nitrogen levels are normal in Dox treated mice
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 show a modest kidney phenotype, with mild tubule dilatations
|
|
• mice treated with Dox at P28 for 2 weeks and analyzed at 41-42 weeks of age show slow development of kidney cysts
• mice treated with Dox at P0 and analyzed at P14 show a modest kidney phenotype, with a few cysts
• however, blood urea nitrogen levels are normal in Dox treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice continue to increase their body weight when switched to a doxycycline (Dox)-containing diet, although not at the same extent as wild-type mice thus showing a partial reversal of weight loss
|
| N |
• size of adipocytes is epididymal white adipose tissue (eWAT), subcutaneous white adipose tissue (sWAT), and in interscapular brown adipose tissue (BAT)is normal in Dox-treated mice
• adipose tissue uridine content is not increased and thus rescued in Dox-treated mice compared to Tg(tetO-Xbp1_is)#Pesch/0 Tg(Adipoq-rtTA)2Zvw/0 mice
|
| N |
• adipose tissue uridine content is not increased and thus rescued in Dox-treated mice compared to Tg(tetO-Xbp1_is)#Pesch/0 Tg(Adipoq-rtTA)2Zvw/0 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD45+ leukocyte infiltration is seen in the sub-conjunctival stroma 3-4 days after eyelid opening, at P16, of pups treated with doxycycline
|
|
• epithelial cells of the ocular surface of pups treated with doxycycline (via nursing moms) are hyperplastic and aberrantly desquamated from the conjunctiva
|
|
• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction
|
|
• the aberrantly desquamated cells within the conjunctival sac are composed of conjunctival epithelial cells and basal cells of stratified epithelia but not corneal epithelial cells, indicating aberrant conjunctival, but not corneal, epithelial cell desquamation
• conjunctival epithelia from pups treated with doxycycline (via nursing moms) exhibit an increase in cell proliferation
|
|
• pups treated with doxycycline (via nursing moms) do not show signs of goblet cell differentiation from the conjunctival epithelium at P9 or P16 unlike controls
|
|
• adult mice administered doxycycline at P90 exhibit loss of goblet cells from the conjunctiva and cellular debris in the conjunctival sac
|
|
• pups from nursing moms administered doxycycline do not exhibit clear conjunctival sacs at P9 as in wild-type pups and instead have a mass of cell debris that is abnormally present in the conjunctival sac, indicating early ocular surface morphogenesis alterations
• adult mice administered doxycycline at P90 exhibit cellular debris in the conjunctival sac
|
|
• pups treated with doxycycline exhibit epidermal metaplasia of corneal epithelium at P16
|
|
• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction
|
|
• pulse doxycycline induction from P0 to P16 results in mutants with severe ulceration and neovascularization in the cornea, even after 180 days post-doxycycline induction
|
|
• CD45+ leukocyte infiltration is seen in the sub-conjunctival stroma 3-4 days after eyelid opening, at P16, of pups treated with doxycycline
|
|
• adult mice administered doxycycline at P90, exhibit hair loss one month after doxycycline induction, with random alopecia on the body, including the eyelid within 3 months
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| keratoconjunctivitis sicca | DOID:12895 | J:194073 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal neonatal survival
|
|
• reduced pulmonary capillary formation in doxycycline-treated mice
|
|
• at E18.5, doxycycline-treated mice exhibit reduced terminal sacs and thickened surrounding mesenchyme in the peripheral lung compared with control mice
• larger but fewer sacs at P1 in doxycycline-treated mice
• however, morphology at P14 and P30 is normal
|
|
• at E18.5 in doxycycline-treated mice
|
|
• impaired epithelial cell differentiation in doxycycline-treated mice
|
|
• at P1, but not P30, in the lungs of doxycycline-treated mice
|
|
• reduced pulmonary capillary formation in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at P50 doxycycline-treated mice exhibit loss of bulge stem cells unlike in control mice
• however, bulge stem cells are present at P20 and P22
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice do not exhibit perinatal toxicity
|
| N |
• doxycycline-treated mice do not exhibit lung pathology or dysfunction
• doxycycline-treated mice exhibit minimal focal airspace enlargement unlike Tg(Scgb1a1-rtTA)1Jaw mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• capillary loops extend into the cornea
|
|
• in mice exposed to deoxycycline treatment at E16.5
|
|
• lymphatic vasculature develops in the corneal limbus
|
|
• capillary loops extend into the cornea
|
|
• enlarged
|
|
• increased anterior chamber depth
|
|
• eyes begin to protrude by 21 to 28 days of age
• difficulty closing eyelids by 8 weeks of age
|
|
• reduced thickness of retinal cell layer
|
|
• reduced thickness
|
|
• becoming worse toward periphery
|
|
• in mice exposed to deoxycycline treatment at E16.5
|
|
• elevated
|
|
• severely impaired vision
|
|
• lymphatic vessels are sparse in the dermis of the ear
• abnormal branching of lymphatic vessels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in mice exposed to deoxycycline treatment at E16.5
|
|
• enlarged
|
|
• increased anterior chamber depth
|
|
• eyes begin to protrude by 21 to 28 days of age in mice exposed to deoxycycline treatment at E16.5
• difficulty closing eyelids by 8 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal bone formation and osteoblast surface/numbers
|
|
• decreased proliferation of osteoclast precursors
|
|
• at 6 months
|
|
• at 6 months
|
|
• more trabecular bone and bone surface at 6 months
|
|
• at 6 months
|
|
• with reduced spacing at 6 months
|
|
• at 6 months
|
|
• decreased proliferation of osteoclast precursors
|
|
• decreased proliferation of osteoclast precursors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal numbers of osteoblasts, bone formation and bone mineral apposition rates
|
|
• in doxycycline-treated mice
|
|
• doxycycline-treated bone marrow cultures exhibit reduced osteoclast precursor proliferation compared with control cultures
|
|
• decreased bone surface in doxycycline-treated mice
|
|
• trabecular, cortical and total in doxycycline-treated mice
|
|
• with increased spacing in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• doxycycline-treated bone marrow cultures exhibit reduced osteoclast precursor proliferation compared with control cultures
|
|
• in doxycycline-treated mice
|
|
• doxycycline-treated bone marrow cultures exhibit reduced osteoclast precursor proliferation compared with control cultures
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice
|
|
• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice
|
|
• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice
|
|
• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal bone formation and numbers of osteoblasts
|
|
• impaired in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• as early as P15 in doxycycline-treated mice
• 27-fold from 10 months of age in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• 4.6-fold increase in trabecular bone surface and a smaller bone surface to bone volume in doxycycline-treated mice
|
|
• trabecular, cortical and total volume as early as P15 in doxycycline-treated mice
|
|
• 3.6-fold with reduced trabecular separation in doxycycline-treated mice
|
|
• 8.5-fold in doxycycline-treated mice
|
|
• severe in doxycycline-treated mice
• in mice following adult onset activation with doxycycline
|
|
• in doxycycline-treated mice
|
|
• impaired in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• at 4 months in doxycycline-treated mice
|
|
• at 10 months in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• gradual in doxycycline-treated mice
|
|
• impaired in doxycycline-treated mice
|
|
• impaired in doxycycline-treated mice
|
|
• in doxycycline-treated mice
|
|
• gradual in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice retain hair follicle stem cells in early telogen and anagen
|
|
• hair phenotype in doxycycline-treated mice appears more slowly than in Dicer1tm1Smr/Dicer1tm1Smr Tg(KRT5-rtTA)1Glk Tg(tetO-cre)1Jaw mice
|
|
• failure of hair regrowth in doxycycline-treated mice
• failure of regression at P20 in doxycycline-treated mice and remained in an abnormal growth phase
• following hair plucking, doxycycline-treated mice fail to sustain hair growth unlike control mice
|
|
• external hair becomes wavy between P12 and P14 in doxycycline-treated mice
|
|
• in doxycycline-treated mice likely due to matrix cell apoptosis
|
|
• at P17 in doxycycline-treated mice after degradation begins
|
|
• fewer differentiation cell in doxycycline-treated mice following plucking-induced anagen initiation
|
|
• with extrusion of abnormally keratinized cellular material in doxycycline-treated mice
|
|
• in doxycycline-treated mice following plucking-induced anagen initiation
|
|
• failure of catagen in doxycycline-treated mice
|
|
• failure of regression at P20 in doxycycline-treated mice
|
|
• by P20, doxycycline-treated mice exhibit thickened interfollicular epidermis compared with control mice
|
|
• mice treated with doxycycline exhibit a temporary phenotype of dry scaly skin that is resolved in an anterior-posterior direction
|
|
• mice treated with doxycycline exhibit a temporary phenotype of dry scaly skin that is resolved in an anterior-posterior direction
|
|
• doxycycline-treated mice exhibit matrix cell apoptosis with DNA damage response unlike in control mice
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 2 and 3 weeks of age likely from airway obstruction and asphyxiation
|
|
• 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
|
|
• mice exhibit decreased lung wet/dry ratio compared with control mice
• however, treatment with amiloride improves lung defects
|
|
• mice exhibit cystic fibrosis-like defects unlike control mice
|
|
• mice exhibit increased nonciliated mucus secreting (mostly goblet) cells in the trachea unlike control mice
|
|
• mice exhibit increased nonciliated mucus secreting (mostly goblet) cells in the trachea unlike control mice
|
|
• airway periciliary liquid layer in the trachea is decreased in height compared to in control mice
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals exposed to doxycycline from E6.5 die within a few hours of birth from respiratory failure
|
|
• severely reduced density of lung capillary network in newborn animals exposed to doxycycline from E6.5, associated with reduced VEGF expression in mutant lungs
|
|
• areas of thin lung mesenchyme and upregulation of integrin alpha 3 (Lama5 receptor) in newborn animals exposed to doxycycline from E6.5
|
|
• areas of thin lung mesenchyme in newborn animals exposed to doxycycline from E6.5
|
|
• total lung parenchyma is reduced
|
|
• airspaces of newborn animals exposed to doxycycline from E6.5 are filled with amorphous proteinaceous material and cellular debris not seen in controls
|
|
• delayed or impaired differentiation of distal alveolar epithelium in newborn animals exposed to doxycycline from E6.5
• mutant peripheral airspaces are often lined with cuboidal epithelium
|
|
• virtual absence of alveolar type I cells in newborn animals exposed to doxycycline from E6.5
|
|
• significant reduction of alveolar type II cells in newborn animals exposed to doxycycline from E6.5
|
|
• enlarged distal airspaces in newborn animals exposed to doxycycline from E6.5
|
|
• newborn animals exposed to doxycycline from E6.5 display labored breathing
|
|
• severely reduced density of lung capillary network in newborn animals exposed to doxycycline from E6.5, associated with reduced VEGF expression in mutant lungs
|
|
• in lungs of newborn animals exposed to doxycycline starting at E6.5
|
|
• in lungs of newborn animals exposed to doxycycline from E6.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• underdeveloped from E11.5
• deficiency in proximodistal outgrowth at E12.5
• smaller in size at E15.5 with a lack in mesenchymal patterning
|
|
• at E11.0, genital mesenchyme exhibits a reduction in cell proliferation compared with in wild-type mice
• however, apoptosis rates are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• with doxycycline induction from P8, hair follicles contain numerous apoptotic cells (more than in mutants with transgenic expression of Dkk1, or Dkk1 and Kremen
|
|
• with doxycline induction from P30, mutants completely lack external hair when examined at P100-102
|
|
• with doxycycline induction from P8 hair follicles in mutants display structural defects at P24, including widened infundibulum and loss of a clearly distinguishable secondary hair germ
|
|
• with doxycycline induction from P8 hair follicles display a widened infundibulum at P24
|
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• with doxycycline induction from P30, hair follicles are mainly absent in mutants
|
|
• with doxycycline induction from P30, hair follicles degrade and form utricles by P180
|
|
• when doxycline induction is performed at P4 or P7 and dorsal skin harvested at P8 or P14, hair follicles in treated skin show cessation of anagen
• with doxycycline induction from P50 and hair plucking at P54, proliferation of secondary hair germ cells of follicles is decreased or absent and a new hair growth phase is not observed by P57
• with induction from P17 (catagen phase), follicles fail to enter anagen
|
|
• when doxycline induction is performed at P4 or P7 and dorsal skin harvested at P8 or P14, hair follicles in treated skin show entry into a premature regression phase compared to controls
|
|
• dermal papillary cells are observed 'stranded' in the epidermis or at the end of 'streamers' of degenerating hair follicles
|
|
• when doxycline induction is performed from P4 to P60, enlargement of intercellular spaces and some cell membrane protrusions are observed in some areas of mutant skins
|
|
• when doxycline induction is performed from P4 to P60, expansion of the basal layer is observed
|
|
• when doxycline induction is performed from P4 to P60, expansion of the suprabasal layer is observed
|
|
• when doxycline induction is performed from P4 to P60, some keratinocytes display long membranous protrusions
|
|
• when doxycline induction is performed from P4 to P60, epidermis displays thickening and hyperproliferation
• with doxycycline induction from P30, epidermis is thickened at P100
|
|
• with doxycycline induction from P8, hair follicles contain numerous apoptotic cells (more than in mutants with transgenic expression of Dkk1, or Dkk1 and Kremen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased phosphatidylcholine in the bronchoalveolar lavage fluid of doxycycline-treated mice
|
|
• in the bronchoalveolar lavage fluid of doxycycline-treated mice
|
|
• increased surfactant protein A, B, C and D in the whole lung lysate of doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit a severe cystic phenotype
• however, mice treated with Dox at P28 and analyzed at 18 weeks of age show amelioration of the cystic phenotype with no difference in cystic index
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts
• however, mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks of age show no differences in kidney weight/body weight ratio
|
|
• mice treated with Dox at P0 show increased blood urea nitrogen levels at P14
• however, mice treated with Dox at P28 and analyzed at 18 weeks of age show no differences in blood urea nitrogen levels
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit a severe cystic phenotype
• however, mice treated with Dox at P28 and analyzed at 18 weeks of age show amelioration of the cystic phenotype with no difference in cystic index
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts
• however, mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks of age show no differences in kidney weight/body weight ratio
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 show development of kidney cysts, with increased kidney weight/body weight ratio and more numerous and larger cysts than single conditional Tulp3 homozygotes
• however, mice treated with Dox at P28 and analyzed at 18 weeks of age show amelioration of the cystic phenotype with no difference in cystic index
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 show increased kidney weight/body weight ratio due to cysts
• mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks of age show a modest elevation of kidney weight/body weight ratio
|
|
• mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks of age show larger tubule dilations
|
|
• mice treated with Dox at P0 show elevated blood urea nitrogen levels
• however, mice treated with Dox at P28 and analyzed at 18 weeks of age show no differences in blood urea nitrogen levels
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 show development of kidney cysts, with increased kidney weight/body weight ratio and more numerous and larger cysts than single conditional Tulp3 homozygotes
• however, mice treated with Dox at P28 and analyzed at 18 weeks of age show amelioration of the cystic phenotype with no difference in cystic index
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 show increased kidney weight/body weight ratio due to cysts
• mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks of age show a modest elevation of kidney weight/body weight ratio
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 do not form kidney cysts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with Dox at P0 and analyzed at P14 exhibit a severe cystic phenotype
• mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks develop severe cystic kidneys
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts
• mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks exhibit increased kidney weight/body weight ratio due to cysts
|
|
• mice treated with Dox at P0 show increased blood urea nitrogen levels at P14
• mice treated with Dox at P28 for 2 weeks show increased blood urea nitrogen levels at 18 weeks of age
|
|
• mice treated with Dox at P0 and analyzed at P14 exhibit a severe cystic phenotype
• mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks develop severe cystic kidneys
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts
• mice treated with Dox at P28 for 2 weeks and analyzed at 18 weeks exhibit increased kidney weight/body weight ratio due to cysts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit a severe cystic phenotype
• mice treated with Dox a P28 for 2 weeks and analyzed at 18 weeks show an intermediate cystic phenotype, with cystic index lower than conditional Pkd1 homozygotes but higher than in double Tulp3 and Pkd1 homozygotes
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts
• mice treated with Dox a P28 for 2 weeks and analyzed at 18 weeks show an intermediate kidney weight/body weight ratio, with lower ratio than conditional Pkd1 homozygotes but higher ratio than in double Tulp3 and Pkd1 homozygotes
|
|
• mice treated with Dox at P0 show increased blood urea nitrogen levels at P14
• mice treated with Dox a P28 for 2 weeks and analyzed at 18 weeks show an intermediate level of blood urea nitrogen, with lower level than conditional Pkd1 homozygotes but higher level than in double Tulp3 and Pkd1 homozygotes
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit a severe cystic phenotype
• mice treated with Dox a P28 for 2 weeks and analyzed at 18 weeks show an intermediate cystic phenotype, with cystic index lower than conditional Pkd1 homozygotes but higher than in double Tulp3 and Pkd1 homozygotes
|
|
• mice treated with doxycycline (Dox) at P0 and analyzed at P14 exhibit increased kidney weight/body weight ratio due to cysts
• mice treated with Dox a P28 for 2 weeks and analyzed at 18 weeks show an intermediate kidney weight/body weight ratio, with lower ratio than conditional Pkd1 homozygotes but higher ratio than in double Tulp3 and Pkd1 homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in P60 animals, hair follicle structures are retained in absence of external hair, but display abnormalities including cyst formation
|
|
• cre induction at P4 causes hair follicle regression by P14 without loss of bulge stem cell markers
|
|
• when doxycline induction is performed from P4 to P18, epidermis exhibits increased proliferation as well as expanded expression of basal and suprabasal markers and hyperproliferation markers
• when doxycline induction is performed from P4 to P18, enlargement of intercellular spaces and some cell membrane protrusions are observed in some areas of mutant skins at P60
• defects of the interfollicular epidermis similar to those observed in conditional Ctnnb1 mutants are seen in induced mutants
|
|
• with doxycycline induction from P4-P18, mast cell number in the dermis is increased at P60
|
|
• with doxycycline induction from P4-P18, mast cell number in the dermis is increased at P60
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice retain hair follicle stem cells in early telogen and anagen
|
|
• hair phenotype in doxycycline-treated mice appears more rapidly than in Droshatm1Litt/Droshatm1Litt Tg(KRT5-rtTA)1Glk Tg(tetO-cre)1Jaw mice
|
|
• failure of hair regrowth in doxycycline-treated mice
• failure of regression at P20 in doxycycline-treated mice and remained in an abnormal growth phase
• following hair plucking, doxycycline-treated mice fail to sustain hair growth unlike control mice
|
|
• external hair becomes wavy between P12 and P14 in doxycycline-treated mice
|
|
• in doxycycline-treated mice likely due to matrix cell apoptosis
|
|
• at P17 in doxycycline-treated mice after degradation begins
|
|
• fewer differentiation cell in doxycycline-treated mice following plucking-induced anagen initiation
|
|
• at P59 doxycycline-treated mice exhibit loss of bulge stem cells unlike in control mice
• however, bulge stem cells are present at P20 and P22
|
|
• with extrusion of abnormally keratinized cellular material in doxycycline-treated mice
|
|
• in doxycycline-treated mice following plucking-induced anagen initiation
|
|
• failure of catagen in doxycycline-treated mice
|
|
• failure of regression at P20 in doxycycline-treated mice
|
|
• by P20, doxycycline-treated mice exhibit thickened interfollicular epidermis compared with control mice
|
|
• mice treated with doxycycline exhibit a temporary phenotype of dry scaly skin that is resolved in an anterior-posterior direction
|
|
• mice treated with doxycycline exhibit a temporary phenotype of dry scaly skin that is resolved in an anterior-posterior direction
|
|
• doxycycline-treated mice exhibit matrix cell apoptosis with DNA damage response unlike in control mice
|
|
• in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• death in the early postnatal period
|
|
• with doxycycline treatment beginning at E6.5, a dramatic lung branching defect is observed
• at E16.5, lungs show even more severe defects than in Kras:Meox2-cre embryos, with large epithelial-lined pouches in place of finely branched network of airways seen in wild-type
• branching defect persists through late gestation leading to early postnatal lethality
|
|
• branching defect originates in epithelium rather than mesenchyme
|
|
• markers of ciliated and Clara cells in the bronchi are significantly reduced at E18.5 compared to controls, indicating block in differentiation of lung epithelium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no response is seen to the antidepressant desipramine in mutants when doxycycline treatment is stopped at 3 months of age
|
|
• contextual learning is impaired in mutants when doxycycline treatment is stopped at 3 months of age compared to mutant littermates maintained on doxycycline
• contextual learning is virtually absent in mutants when no doxycycline treatment is given throughout development
|
|
• cued learning is normal in mutants when doxycycline treatment is stopped at 3 months of age but impaired when no doxycycline treatment is given throughout development
|
|
• mutants bred without doxycycline treatment are hyperactive compared to mutants bred with doxycycline treatment
• hyperactivity is not seen when doxycycline treatment is stopped at 3 months of a
|
|
• long term potentiation is impaired requiring a greater amplitude stimulus to evoke any response in mutants when doxycycline treatment is stopped at 3 months of age compared to mutant littermates maintained on doxycycline
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• alpha cells in diphtheria-treated mice transdifferentiate into beta cells
|
|
|
• alpha cells in diphtheria-treated mice transdifferentiate into beta cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when treated with doxycycline at P25
|
|
• fail to extend when treated with doxycycline in early postnatal life
• regression of sweat glands when treated with doxycycline at P20
|
|
• elevated lipid production when treated with doxycycline at P25
|
|
• when treated with doxycycline at P20
|
|
• minitaturized when treated with doxycycline at P25
|
|
• delayed initiation of anagen until P29, when treated with doxycycline at P18
|
|
• premature when treated with doxycycline at P9
• however, hair follicle regression isnt observed when treated with doxycycline at P25
|
|
• slightly reduced proliferation when treated with doxycycline at P25
|
|
• flattened surface when treated with doxycycline in early postnatal life
|
|
• progressive from P7 when treated with doxycycline in early postnatal life
|
|
• progressive from P7 when treated with doxycycline in early postnatal life
|
|
• miniaturized when treated with doxycycline in early postnatal life
• decreased taste bud in fungiform and circumvallate papillae when treated with doxycycline in early postnatal life
|
|
• decreased basal cell proliferation in the filiform papillae and plantar epithelium, fungiform and circumvallate taste buds and sweat buds when treated with doxycycline at in either the early postnatal period, or in adult life
|
|
• miniaturized when treated with doxycycline in early postnatal life
• decreased taste bud in fungiform and circumvallate papillae when treated with doxycycline in early postnatal life
|
|
• flattened surface when treated with doxycycline in early postnatal life
|
|
• progressive from P7 when treated with doxycycline in early postnatal life
|
|
• progressive from P7 when treated with doxycycline in early postnatal life
|
|
• miniaturized when treated with doxycycline in early postnatal life
• decreased taste bud in fungiform and circumvallate papillae when treated with doxycycline in early postnatal life
|
|
• when treated with doxycycline at P25
|
|
• fail to extend when treated with doxycycline in early postnatal life
• regression of sweat glands when treated with doxycycline at P20
|
|
• elevated lipid production when treated with doxycycline at P25
|
|
• when treated with doxycycline at P20
|
|
• flattened surface when treated with doxycycline in early postnatal life
|
|
• progressive from P7 when treated with doxycycline in early postnatal life
|
|
• progressive from P7 when treated with doxycycline in early postnatal life
|
|
• miniaturized when treated with doxycycline in early postnatal life
• decreased taste bud in fungiform and circumvallate papillae when treated with doxycycline in early postnatal life
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• doxycycline-treated mice exhibit normal neonatal survival
|
|
• reduced pulmonary capillary formation in doxycycline-treated mice
|
|
• doxycycline-treated mice exhibit enlarged airspaces with fewer number of saccules and reduced epithelial cell differentiation compared with control mice
|
|
• in the lungs of doxycycline-treated mice
|
|
• reduced pulmonary capillary formation in doxycycline-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all newborn mice exposed to doxycycline from E6.5 to E7.5 die within 10 min of delivery
• all mice exposed to doxycycline at either E10.5 or E12.5 and continuing until birth (E18.5 to E19.5) exhibit neonatal lethality
|
|
• only 10% of mice exposed to doxycycline from E16.5 to term exhibit neonatal death
• neonatal viability is also significantly reduced when doxycycline is administered between E8.5 and E12.5
|
|
• capillary leakage and macrophage accumulation within the alveolar space of doxycycline-exposed newborn mice
|
|
• pulmonary congestions in perinatal lung sections from doxycycline-exposed mice
|
|
• at E19.5 (birth), dilation of peripheral lung saccules is reduced and the septa remain thickened in doxycycline-exposed mice
|
|
• in doxycycline-exposed mice, type II alveolar cells display Golgi complex abnormalities, aberrant lamellar body formation, fewer and shorter apical microvilli, and freqeunt accumulation of lipid droplets consistent with increased pulmonary triglyceride levels
• in contrast, the ultrastructure of type I alveolar cells remains normal
|
|
• fewer secretary vesicles or mature lamellar bodies in doxycycline-exposed mice
|
|
• at E19.5 (birth), the number of type II alveolar cells is markedly reduced in the terminal lung saccules of all doxycycline-exposed mice
|
|
• nondilated alveolar saccules in doxycycline-exposed newborn mice
|
|
• in doxycycline-exposed mice, alveolar walls are thickened but still lined with organized type I and type II cells
|
|
• focal or extensive atelectasis seen in perinatal lung sections from mice exposed to doxycycline from E6.5 to E7.5
• all neonatal lungs from mice exposed to doxycycline from E6.5 to E7.5 fail to inflate and sink in saline, unlike wild-type neonatal lungs
• however, lungs of viable mice exposed to doxycycline from E16.5 to term appear inflated and show normal lung morphology
|
|
• hyaline membrane formation seen in perinatal lung sections from mice exposed to doxycycline from E6.5 to E7.5
|
|
• all mice exposed to doxycycline from E6.5 to E7.5 develop severe respiratory distress immediately after birth
• also seen in all mice exposed to doxycycline at either E10.5 or E12.5 and continuing until birth (E18.5 to E19.5)
|
|
• the phosphatidylcholine (PtdCho) content is significantly reduced when doxycycline is administered between E8.5 and E12.5 or between E12.5 and E16.5, but not prior to E9.5
• at E17.5, the PtdCho content is significantly reduced in mice exposed to doxycycline from E0 to E17, with a severe decrease in the proportion of dipalmitoyl-PtdCho, suggesting a selective depletion of the C16:0 fatty acid; however, neither phosphatidylethanolamine nor cholesterol is significantly reduced
• total BAL fluid contains significantly less phospholipid per lung; both the large (LA) and small (SA) aggregate fractions are severely depleted in total phospholipid
• the reduction in surfactant protein is less than that in total phospholipid resulting in a 4.7-, 2.8-, and 7.4-fold increase in the protein:phospholipid ratio in BAL, LA, and SA, respectively
|
|
• in mice exposed to doxycycline from E0 to E17, phosphatidylcholine (PtdCho) formation is blocked and surfactant fatty acid synthesis is shunted into the triglyceride pool
• surfactant protein SP-A, SP-C, and SP-D levels are significantly reduced, whereas SP-B protein content is elevated
|
|
• significantly increased triglyceride levels in neonatal lungs from mice exposed to doxycyclin from E0 to E17, with a similar increase in the proportion of species containing palmitic acid (C16:0), esp. in the species containing 48 and 60 carbons
|
|
• capillary leakage and macrophage accumulation within the alveolar space of doxycycline-exposed newborn mice
|
|
• pulmonary congestions in perinatal lung sections from doxycycline-exposed mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die shortly after birth when doxycycline is administered throughout gestation
• in the absence of doxycycline treatment mutants are viable
|
|
• lung and airway malformations are seen when doxycycline exposure occurs between E0.5 and E13.5
• doxycycline exposure after E13.5 does not result in any pulmonary or extrapulmonary abnormalities
|
|
• branching morphogenesis is abnormal with doxycycline treatment
|
|
• lungs are hypoplastic after doxycycline exposure
|
|
• peripheral tubule dilation is seen with doxycycline exposure
|
|
• tracheal abnormalities are seen
• doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities
|
|
• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
|
|
• fewer cartilaginous rings are seen with doxycycline treatment
|
|
• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
|
|
• fewer cartilaginous rings are seen with doxycycline treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die shortly after birth when doxycycline is administered throughout gestation
• in the absence of doxycycline mutants are viable
|
|
• lung and airway malformations are seen when doxycycline exposure occurs between E0.5 and E13.5
• doxycycline exposure after E13.5 does not result in any pulmonary or extrapulmonary abnormalities
|
|
• cysts that contain neuroepithelial cells are seen in the peripheral lung tissue
|
|
• branching morphogenesis is abnormal
|
|
• lungs are hypoplastic when doxycycline is administered throughout gestation
|
|
• peripheral tubule dilation is seen after doxycycline exposure
|
|
• tracheal abnormalities are seen
• doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities
|
|
• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
|
|
• fewer cartilaginous rings are seen after doxycycline exposure
|
|
• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
|
|
• fewer cartilaginous rings are seen after doxycycline exposure
|
|
• cysts that contain neuroepithelial cells are seen in the peripheral lung tissue
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no increase in the number of neutrophils or macrophages in mice treated with doxycycline from E0 through P16
|
|
• goblet cell hyperplasia, associated with the accumulation of both neutral and acidic mucins, in the larger airways of mice treated with doxycycline from E0 through P16
• neither airspace nor alveolar morphological abnormalities were detected
|
|
• increased in mice treated with doxycycline
|
|
• decreased in mice treated with doxycycline
|
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 04/16/2024 MGI 6.23 |
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