behavior/neurological phenotype

• pup cannibalization
  • newborn mice are frequently cannibalized by the mother
  (MGI Ref ID J:93473)

mortality/aging

• postnatal lethality, incomplete penetrance
  • only 46% of mice treated with doxycycline from E0 survive to P5
  (MGI Ref ID J:93473)
  • 50% of mice treated with doxycycline from E0 through P16 died within 30 days of birth
  (MGI Ref ID J:88601)

• neonatal lethality, incomplete penetrance
  • most mice treated with doxycycline from E0 die on P1
  (MGI Ref ID J:93473)

respiratory system phenotype

• abnormal pulmonary alveolus epithelial cell morphology
  • Normal - however, no evidence of capillary leakage or endothelial cell abnormalities are observed
  (MGI Ref ID J:93473)
  • 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
  (MGI Ref ID J:93473)

• abnormal surfactant secretion
  • SP-D mRNAs are significantly increased at E18.5
  (MGI Ref ID J:93473)
  • SP-A, SP-B, and SP-C mRNAs are significantly decreased at E18.5
  (MGI Ref ID J:93473)
  • the active SP-B peptide is markedly decreased in lung homogenates prior to birth
  (MGI Ref ID J:93473)

• absent alveolar lamellar bodies
  (MGI Ref ID J:93473)

• absent type I pneumocytes
  • at E18.5, no squamous type I cells are observed in mice treated with doxycycline from E0
  (MGI Ref ID J:93473)

• dilated respiratory conducting tubes
  • increased airspace in mice prenatally treated with doxycycline
  (MGI Ref ID J:88601)
  • Normal - normal prenatal lung morphogenesis
  (MGI Ref ID J:88601)
  • postnatal treatment with doxycycline also resulted in increased airspace but to a lesser extent
  (MGI Ref ID J:88601)

• increased respiratory mucosa goblet cell number
  • goblet cell hyperplasia, associated with the accumulation of both neutral and acidic mucins, observed in mice treated with doxycycline from E0 through P16
  (MGI Ref ID J:88601)

• abnormal type II pneumocyte morphology
  • at E18.5, mice treated with doxycycline from E0 show absence of lamellar bodies in alveolar type II cells
  (MGI Ref ID J:93473)

• pulmonary hyaline membrane formation
  • mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display hyaline membrane formation
  (MGI Ref ID J:93473)

• atelectasis
  • mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display focal or extensive atelectasis
  (MGI Ref ID J:93473)

• respiratory distress
  • ~50% of mice treated with doxycycline from E0 develop severe respiratory distress within 2-3 hrs of birth
  (MGI Ref ID J:93473)

• impaired lung alveolus development
  (MGI Ref ID J:93473)
  • 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
  (MGI Ref ID J:88601)

• decreased surfactant secretion
  • at E18.5, no secreted surfactant is detected in the air spaces of mice treated with doxycycline from E0
  (MGI Ref ID J:93473)

• abnormal lung saccule morphology
  • at E18.5, mice treated with doxycycline from E0 display immature peripheral lung saccules, resembling those normally seen at E16-E17
  (MGI Ref ID J:93473)

• abnormal pulmonary alveolus wall morphology
  • at E18.5, mice treated with doxycycline from E0 show thickened alveolar walls lined by immature cuboidal type II cells
  (MGI Ref ID J:93473)

• abnormal surfactant composition
  • 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
  (MGI Ref ID J:93473)

• pulmonary vascular congestion
  • mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion
  (MGI Ref ID J:93473)

cardiovascular system phenotype

• pulmonary vascular congestion
  • mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion
  (MGI Ref ID J:93473)

hematopoietic system phenotype

• increased neutrophil cell number
  • observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
  (MGI Ref ID J:88601)

• increased macrophage cell number
  • observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
  (MGI Ref ID J:88601)

homeostasis/metabolism phenotype

• cyanosis
  • ~50% of mice treated with doxycycline from E0 display cyanosis
  (MGI Ref ID J:93473)

immune system phenotype

• increased macrophage cell number
  • observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
  (MGI Ref ID J:88601)

• increased neutrophil cell number
  • observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16
  (MGI Ref ID J:88601)

behavior/neurological phenotype

• seizures
  (MGI Ref ID J:70409)

mortality/aging

• postnatal lethality, complete penetrance
  • mutant animals die between P9 and P12
  (MGI Ref ID J:70409)

nervous system phenotype

• seizures
  (MGI Ref ID J:70409)

endocrine/exocrine gland phenotype

• abnormal pancreatic beta cell morphology
  • pancreatic beta cells are present, but have abnormal morphology
  (MGI Ref ID J:70409)

• abnormal insulin secretion
  • beta cells exhibit dysregulated insulin secretion
  (MGI Ref ID J:70409)

• disorganized pancreatic islets
  • disorganized morphology with non-beta cells present in the core
  (MGI Ref ID J:70409)

growth/size/body region phenotype

• postnatal growth retardation
  • mutant animals are smaller than controls at P8
  (MGI Ref ID J:70409)

homeostasis/metabolism phenotype

• decreased circulating glucagon level
  • level was 5 fold less in mutant mice than in control animals
  (MGI Ref ID J:70409)

• abnormal insulin secretion
  • beta cells exhibit dysregulated insulin secretion
  (MGI Ref ID J:70409)

• hypoglycemia
  • described as severe in mutant animals
  (MGI Ref ID J:70409)

• increased circulating insulin level
  • the plasma insulin level was very high considering the low glucose levels in mutant animals
  (MGI Ref ID J:70409)

• increased glycogen level
  • mutant mice have a 2.5-fold higher glycogen content than controls
  (MGI Ref ID J:70409)

mammalian phenotype

• immune system phenotype
  • Normal - no increase in the number of neutrophils or macrophages in mice treated with doxycycline from E0 through P16
  (MGI Ref ID J:88601)

respiratory system phenotype

• increased respiratory mucosa goblet cell number
  • neither airspace nor alveolar morphological abnormalities were detected
  (MGI Ref ID J:88601)
  • 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
  (MGI Ref ID J:88601)

• decreased lung compliance
  • decreased in mice treated with doxycycline
  (MGI Ref ID J:88601)

• increased airway resistance
  • increased in mice treated with doxycycline
  (MGI Ref ID J:88601)

• abnormal respiratory mechanics
  (MGI Ref ID J:88601)

normal phenotype

• no abnormal phenotype detected
  • Normal - homozygous mice exhibit no discernable phenotype; mice are viable and fertile
  (MGI Ref ID J:63039)

normal phenotype

• no abnormal phenotype detected
  • Normal - homozygous mice exhibit no discernable phenotype; mice are viable and fertile with normal liver metabolism and normal glucose homeostasis
  (MGI Ref ID J:63039)