All Phenotypes Pcyt1a<tm1Irt> MGI Mouse

neonatal lethality, complete penetrance ( J:118292 )

• 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

neonatal lethality, incomplete penetrance ( J:118292 )

• 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

abnormal lung vasculature morphology ( J:118292 )

• capillary leakage and macrophage accumulation within the alveolar space of doxycycline-exposed newborn mice

pulmonary vascular congestion ( J:118292 )

• pulmonary congestions in perinatal lung sections from doxycycline-exposed mice

abnormal lung saccule morphology ( J:118292 )

• at E19.5 (birth), dilation of peripheral lung saccules is reduced and the septa remain thickened in doxycycline-exposed mice

abnormal type II pneumocyte morphology ( J:118292 )

• 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

decreased alveolar lamellar body number ( J:118292 )

• fewer secretary vesicles or mature lamellar bodies in doxycycline-exposed mice

decreased type II pneumocyte number ( J:118292 )

• at E19.5 (birth), the number of type II alveolar cells is markedly reduced in the terminal lung saccules of all doxycycline-exposed mice

abnormal pulmonary alveolar sac morphology ( J:118292 )

• nondilated alveolar saccules in doxycycline-exposed newborn mice

increased pulmonary alveolus wall thickness ( J:118292 )

• in doxycycline-exposed mice, alveolar walls are thickened but still lined with organized type I and type II cells

atelectasis ( J:118292 )

• 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

pulmonary hyaline membrane formation ( J:118292 )

• hyaline membrane formation seen in perinatal lung sections from mice exposed to doxycycline from E6.5 to E7.5

respiratory distress ( J:118292 )

• 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)

abnormal surfactant composition ( J:118292 )

• 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

abnormal surfactant secretion ( J:118292 )

• 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

cyanosis ( J:118292 )

• all newborn mice exposed to doxycycline from E6.5 to E7.5 become cyanotic

increased triglyceride level ( J:118292 )

• 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

abnormal lung vasculature morphology ( J:118292 )

• capillary leakage and macrophage accumulation within the alveolar space of doxycycline-exposed newborn mice

pulmonary vascular congestion ( J:118292 )

• 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

Contributing Projects: 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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