Phenotypes for Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-IL1B)KBry MGI:5444503 MGI Mouse

postnatal lethality, incomplete penetrance ( J:130523 )

• about 50% of newborns from females provided with doxycycline during pregnancy and lactation die before 7 days of age

• pups from females provided with doxycycline during pregnancy and lactation weight about 36% less than controls

postnatal growth retardation ( J:130523 )

• postnatal growth of newborns from females provided with doxycycline during pregnancy and lactation is decreased

abnormal lung vasculature morphology ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation exhibit abnormal vascular development of the lungs, showing capillaries of varying sizes scattered within the thick septa at P3 compared to control lungs that show capillaries lining the alveolar septa, and by P14, capillaries are dysmorphic

lung inflammation ( J:107601 , J:130523 )

• mutants administered doxycycline for 8 days show a 6- to 12-fold increase in the total number of inflammatory cells in bronchoalveolar lavage fluid, mainly due to an influx of neutrophils into the lung; most of the remaining cells are macrophages (J:107601)

• an increase in inflammatory cells is seen in the alveoli and parenchyma of lungs in mutants administered doxycycline for 5 weeks (J:107601)

• however, lung histology is normal in mutants not given doxycycline (J:107601)

• fetal and neonatal lungs in mutants from females provided with doxycycline during pregnancy and lactation exhibit neutrophil and macrophage infiltration in airways and airspaces (J:130523)

• number of neutrophils in the lungs increases rapidly from E18.5 to P0 and remains stable after that time, however the number of macrophages continues to increase during the first week of life (J:130523)

abnormal lung alveolus development ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation exhibit disrupted alveolar development, with absence of septation and thus thicker septa of distal airspaces and an increase in alveolar chord length compared to controls

abnormal lung epithelium morphology ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation exhibit thickened epithelium and subepithelial smooth muscle in airway walls, indicating airway remodeling

abnormal pulmonary alveolus morphology ( J:107601 )

• mean alveolar cord length is larger in mutants administered doxycycline for 5 weeks compared to controls

• airway mucus metaplasia in mutants administered doxycycline for 5 weeks

increased pulmonary alveolus wall thickness ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation exhibit increased thickness of saccular/alveolar walls by 23% on P0 and by 38% on P7

overexpanded pulmonary alveolus ( J:107601 )

• severe distal airspace enlargement is seen in mutants administered doxycycline for 5 weeks

thick pulmonary interalveolar septum ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation exhibit thicker septa of distal airspaces

emphysema ( J:107601 )

• mutants administered doxycycline for 5 weeks exhibit distal airspace enlargement consistent with emphysema

abnormal pulmonary elastic fiber morphology ( J:107601 , J:130523 )

• elastin fibers are disrupted, frayed and short in the lungs of mutants administered doxycycline for 5 weeks compared to controls, indicating elastin degradation (J:107601)

• newborns from females provided with doxycycline during pregnancy and lactation exhibit abnormal elastin structure in the distal lung at P7, with poorly organized elastin fibers in the walls of airspaces and lack of elastin in septal crests, and by 3 weeks of age, elastin fibers are splayed and disorganized and are often perpendicular to the airspace wall, have inflammatory cells infiltrating the bundles, and distribution in the blunted secondary crests is abnormal (J:130523)

abnormal bronchiole morphology ( J:107601 )

• bronchiolar thickening and peribronchiolar lymphocytic nodules are seen in mutants administered doxycycline for 5 weeks

pulmonary fibrosis ( J:107601 )

• lung fibrosis with extensive subepithelial fibrosis is seen in mutants administered doxycycline for 5 weeks, with lesions showing increased collagen deposition

increased respiratory mucosa goblet cell number ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation exhibit goblet cell hyperplasia

abnormal lung volume ( J:107601 )

• lung volumes and lung volume/body weight ratios are increased after 5 weeks of doxycycline administration

respiratory failure ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation (fetuses receive doxycycline transplacentally and newborns receive it from the mother's milk) develop respiratory insufficiency within several days after birth

abnormal chemokine level ( J:107601 , J:130523 )

• mutants administered doxycycline for 5 weeks exhibit increased production of CXC chemokines Cxcl1 (KC) and Cxcl2 (MIP-2) (J:107601)

• fetal and neonatal lungs in mutants from females provided with doxycycline during pregnancy and lactation exhibit increased production of chemokines, KC, MIP-2, MCP-1 and MCP-2 (J:130523)