mortality/aging
|
• the 2 pups that survived past birth had to be euthanized by P7
|
|
• 1 of 3 pups died at birth
|
respiratory system
|
• develop large, cyst-like structures at the distal epithelial branch tips that are the result of larger, rounder branch tips
|
|
• cultured lungs from E12.5 embryos show a significant reduction in branching
• branch tips are larger and rounder and lead to large open spaces in the lung
• significant decrease in total lung epithelial cell proliferation at E14.5 resulting from a decrease in proliferation of the distal tip epithelium
|
|
• distal epithelial tips show a range of defects including absence of microvilli, apical membranous blebs and disrupted cell-cell adhesion
• the basal epithelial surface is not uniform and many cells have a rounded appearance with membranous blebs projecting into the subcellular space
• the extracellular matrix and stabilized tubulin appear disrupted at the basal surfaces
|
small lung
(
J:202984
)
|
• noticeable by E14.5 and more significant by E16.5
|
|
• pups that survive birth have difficulty breathing
|
cellular
|
• apparent precocious differentiation of distal tip progenitor cells into type 2 alveolar cells at E14.5
|
|
• migration of epithelial cells from cultured E12.5 lung buds is decreased compared to controls
|
|
• significant decrease in total lung epithelial cell proliferation at E14.5 resulting from a decrease in proliferation of the distal tip epithelium
|
growth/size/body
|
• develop large, cyst-like structures at the distal epithelial branch tips that are the result of larger, rounder branch tips
|


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