Analysis Tools
homeostasis/metabolism
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• normal metabolism; homozygous animals are described as having somewhat reduced blood glucose levels, but these values remained within normal ranges
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• random glucose levels are lower at both 2-3 months and 10-12 months of age
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• plasma glucagon levels are elevated by two orders of magnitude
(J:73926)
• glucagon levels are nearly 200-fold increased at 10-12 months of age
(J:176507)
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• random insulin levels are slightly lower in 10-12 month old mice
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adipose tissue
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• mice have little, if any, subcutaneous fat
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• mice have little, if any, abdominal visceral fat
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cellular
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• marker analysis indicates abnormal alpha cell differentiation
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• proliferation of non-alpha cells (most of which are beta cells) is increased, however no difference is seen in alpha cells
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digestive/alimentary system
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• acinar cells are larger
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endocrine/exocrine glands
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• proliferation of non-alpha cells (most of which are beta cells) is increased, however no difference is seen in alpha cells
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• at 2-3 months of age, mice exhibit normal islet morphology but islets are mostly composed of alpha cells
• islet cell mass is almost 10-fold larger at 5-7 months of age
• islets are irregular in shape in 5-7 month old mice
• mice have numerous small, irregularly-shaped islet cell clusters which are not seen in wild-type mice
• dysplastic islets at 12 months are numerous in non-tumor part of pancreas, and they are often stand-alone and larger compared to dysplastic islets at 5-7 months of age
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• alpha cells are larger
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• marker analysis indicates abnormal alpha cell differentiation
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• islets are larger in 5-7 month old mice
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• islets are hyperplastic and mildly dysplastic at 5-7 months of age
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• some exocrine ducts harbor islet cells in their walls and others are enclosed in islets in a formation called nesidioblastosis along with exocrine acinar cells
• more exocrine ducts are contiguous with budding islets in mutant pancreas than in wild-type
• exocrine ducts harboring glucagon-positive cells are more frequent in mutant than in wild-type pancreata
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• acinar cells are larger
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• pancreas is already larger at 2-3 months of age, being about 2.5-fold larger in 10-12 month old mice
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• at 10-12 months of age, gross pancreatic neuroendocrine tumors (PNETs) are seen in most pancreata and micro-PNETs are seen in all mice
• PNETs are well differentiated and occasionally metastasize to the liver
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• most PNETs are glucagonomas, but some are non-functioning
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growth/size/body
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• pancreas is already larger at 2-3 months of age, being about 2.5-fold larger in 10-12 month old mice
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• mice are lean and are on average 40% lighter than wild-type or heterozygous mice
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• mice fail to gain significant weight after 3 months of age compared to wild-type mice that continue to gain weight throughout 12 months
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integument
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• mice have little, if any, subcutaneous fat
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liver/biliary system
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• liver weighs 17% less than in wild-type mice
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• liver is red in color at 12 months of age compared to wild-type liver which usually appears fatty
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neoplasm
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• at 10-12 months of age, gross pancreatic neuroendocrine tumors (PNETs) are seen in most pancreata and micro-PNETs are seen in all mice
• PNETs are well differentiated and occasionally metastasize to the liver
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• most PNETs are glucagonomas, but some are non-functioning
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