Analysis Tools
mortality/aging
|
• homozygotes can survive until at least 6.5 days post-partum (P6.5), but are not maintained longer for ethical reasons
|
digestive/alimentary system
|
• homozygotes show impaired posterior foregut development
|
|
• homozygotes show a blockage in differentiation of acinar cells
|
|
• homozygotes exhibit normal initial generation and outgrowth of dorsal and ventral pancreatic ducts
• however, at 11.5 dpc, homozygotes lack the discrete outgrowth derived from the ventral pancreatic duct
• also at 11.5 dpc, the dorsal pancreatic outgrowth is replaced by an extra short ductular structure which persists into perinatal stages and undergoes limited proliferation and outgrowth as well as abnormal branching
• this ductular tree lacks insulin and amylase-positive cells and contains glucagons-expressing cells instead
|
|
• at P1, mutant small intestines contain no milky gut contents and appear empty
|
|
• at 18.5 dpc and P1, homozygotes exhibit a malformed stomach/duodenum junction relative to wild-type mice
• in most mutants, the rostral-most duodenum forms an undulated cavity lacking villi, and mature Brunner's glands, with a smooth cuboidal (rather than columnar) epithelium lining that is continuous with the common bile duct and dorsal pancreatic ductule
• a few mutants lack this undulated cavity but still contain abnormal smooth cuboidal epithelium
• 5 of 6 homozygotes show altered gut lumen architecture with a spiraled (rather than fairly straight) tube and several tight lumen constrictions
• just distal to the malformed rostral duodenum, homozygotes contain apparently normal villi, enterocytes and most enteroendocrine cell types; however, the numbers of enteroendocrine cells are markedly reduced in mutant villi
• homozygotes exhibit a "duodenal" gut tube of wild-type length; no extensive cell death is detected at any stage of development
|
|
• at P6.5, many homozygotes display a stomach/duodenal obstruction, as shown by stomach distension and failure of gastric emptying
|
|
• at 18.5 dpc and P1, the mutant pyloric sphincter appears twisted despite normal smooth muscle bands
|
endocrine/exocrine glands
|
• homozygotes show a blockage in differentiation of acinar cells
|
|
• homozygotes exhibit normal initial generation and outgrowth of dorsal and ventral pancreatic ducts
• however, at 11.5 dpc, homozygotes lack the discrete outgrowth derived from the ventral pancreatic duct
• also at 11.5 dpc, the dorsal pancreatic outgrowth is replaced by an extra short ductular structure which persists into perinatal stages and undergoes limited proliferation and outgrowth as well as abnormal branching
• this ductular tree lacks insulin and amylase-positive cells and contains glucagons-expressing cells instead
|
|
• at 11.5 dpc, the common bile duct is severely reduced in size
|
|
• homozygotes show a blockage in differentiation of islets
|
|
• homozygotes show a blockage in differentiation of mature beta-cells
|
|
• at 18.5 dpc, homozygotes display complete lack of pancreatic tissues
• in contrast, the liver, gall bladder, spleen, stomach, common bile duct, and other viscera are present and normal
|
growth/size/body
|
• although P6.5 homozygotes contain milk in their stomachs, they weigh ~60% less than wild-type littermates
|
|
• homozygotes appear normal immediately after birth but show signs of growth retardation as early as P1
|
homeostasis/metabolism
dehydration
(
J:32017
)
|
• homozygotes show signs of dehydration as early as P1
• by P6.5, homozygotes are severely dehydrated
|
liver/biliary system
|
• at 11.5 dpc, the common bile duct is severely reduced in size
|
|
• at 11.5 dpc, the mutant liver primordium is juxtaposed to the duodenum
|
integument
sparse hair
(
J:32017
)
|
• at P6.5, homozygotes have very little fur relative to wild-type mice
|
muscle
|
• at 18.5 dpc and P1, the mutant pyloric sphincter appears twisted despite normal smooth muscle bands
|
cellular
|
• homozygotes show a blockage in differentiation of mature beta-cells
|
