homeostasis/metabolism
• transgenic mice gradually attain an impaired glucose tolerance response to glucose challenge
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endocrine/exocrine glands
• when dams are treated with doxycycline from conception through birth, only small epithelial remnants of the pancreas form; treatment at E7.5 or E8.5 results in the same phenotype
• doxycycline from E9.5 diminishes epithelial morphogenesis; treatement from E9.5 allows outgrowth of a linear epithelial tube with nascent invaginations representing initial primary branching
• treatment from E11.5 allows the formation of a larger crude duct-like structure with a few distal primary branches; treatement from E12.5 permits formation of extensive fine structure consisting of immature acini and associated small ductules
• with treatment from E12.5, pancreatic dorsal and ventral remnants composed of convoluted partially branched duct-like epithelium of columnar epithelium are present, and show a block at the stage of acinar cell formation
• examination of embryo ductal remnants from mice treated with dox from E11.5 show an absence of preacini; treatment from E12.5 results in a larger remnant with a smaller proportion of primitive duct; the epithelium is replaced by numerous eosinophilic clusters lacking ductal markers which are polarized, arranged around a central lumen and resemble immature acini
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• ~1/5 pups are born without a pancreas; rescue of pancreas formation is observed in ~80% of transgenic mice
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