Phenotypes Associated with This Genotype

Genotype
MGI:3036449

cn3

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, incomplete penetrance ( J:93473 )

• most mice treated with doxycycline from E0 die on P1

postnatal lethality, incomplete penetrance ( J:88601 , J:93473 )

• 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)

hematopoietic system

increased neutrophil cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

increased macrophage cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

immune system

increased neutrophil cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

increased macrophage cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

respiratory system

pulmonary vascular congestion ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion

impaired lung alveolus development ( J:88601 , 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 (J:88601)

abnormal lung saccule morphology ( J:93473 )

• at E18.5, mice treated with doxycycline from E0 display immature peripheral lung saccules, resembling those normally seen at E16-E17

abnormal pulmonary alveolus epithelial cell morphology ( 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

• however, no evidence of capillary leakage or endothelial cell abnormalities are observed

absent type I pneumocytes ( J:93473 )

• at E18.5, no squamous type I cells are observed in mice treated with doxycycline from E0

abnormal type II pneumocyte morphology ( J:93473 )

• at E18.5, mice treated with doxycycline from E0 show absence of lamellar bodies in alveolar type II cells

absent alveolar lamellar bodies ( J:93473 )

increased pulmonary alveolus wall thickness ( J:93473 )

• at E18.5, mice treated with doxycycline from E0 show thickened alveolar walls lined by immature cuboidal type II cells

atelectasis ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display focal or extensive atelectasis

dilated respiratory conducting tube ( J:88601 )

• 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

pulmonary hyaline membrane formation ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display hyaline membrane formation

increased respiratory mucosa goblet cell number ( J:88601 )

• goblet cell hyperplasia, associated with the accumulation of both neutral and acidic mucins, observed in mice treated with doxycycline from E0 through P16

respiratory distress ( J:93473 )

• ~50% of mice treated with doxycycline from E0 develop severe respiratory distress within 2-3 hrs of birth

abnormal surfactant composition ( J:93473 )

• 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

abnormal surfactant secretion ( J:93473 )

• 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

decreased surfactant secretion ( J:93473 )

• at E18.5, no secreted surfactant is detected in the air spaces of mice treated with doxycycline from E0

homeostasis/metabolism

cyanosis ( J:93473 )

• ~50% of mice treated with doxycycline from E0 display cyanosis

behavior/neurological

pup cannibalization ( J:93473 )

♀ • newborn mice are frequently cannibalized by the mother

cardiovascular system

pulmonary vascular congestion ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion