Analysis Tools
adipose tissue
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• peri-pancreatic adipocytes exhibit 1.8-fold smaller cell sizes with 2-3-fold more cell numbers than control adipocytes
• peri-pancreatic adipocytes express reduced differentiation markers
• gonadal and subcutaneous inguinal adipocytes show a smaller size at 14 weeks of age without increases in cell numbers
• mice fed a high-fat diet show an even more marked decrease in peri-pancreatic adipocyte cell size and increase in adipose cell numbers
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• peri-pancreatic adipocytes exhibit 1.8-fold smaller cell sizes
• gonadal and subcutaneous inguinal adipocytes show a smaller size at 14 weeks of age without increases in cell numbers
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• reduction in fat pad weight at 14 weeks of age
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behavior/neurological
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• increase in water consumption
• however, food consumption is similar to controls
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cardiovascular system
myocarditis
(
J:228009
)
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• mice exhibit cardiac myocarditis at 14 weeks of age or older
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endocrine/exocrine glands
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• structures of pancreatic islets are disrupted, with increased apoptosis of beta cells after onset of diabetes and more severe at later stages
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• insulin secretion declines after 10 weeks of age
• glucose-stimulated insulin secretion from isolated islets is reduced
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• accumulation of white blood cells invading into islets
• CD8+ T and CD4+ T cells infiltrate into the islets by 12 weeks of age
• MCHII+CD11b+CD11c- macrophages, CD3e+ T cells and CD19+ B cells are increased in the pancreases of mutants
• macrophage infiltration into the pancreas by 14 weeks of age and these macrophages express high levels of proinflammatory cytokines
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growth/size/body
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• lower body weight after onset of diabetes
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homeostasis/metabolism
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• insulin secretion declines after 10 weeks of age
• glucose-stimulated insulin secretion from isolated islets is reduced
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• age-dependent increase in glucose levels
• high-fat diet accelerates hyperglycemia with onset at 8 weeks of age
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• basal and glucose-stimulated insulin levels are reduced
• high-fat diet causes further reduction of insulin levels
• however, insulin tolerance test shows similar insulin responses to controls
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• mice show increased beta-hydroxybutyrate levels in the blood
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• cholesterol levels, but not HDL or FFA, are slightly reduced after 18 weeks of age
• however, mice exhibit normal lipid profiles up to the age of 14 weeks, including total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and free fatty acid
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• triglyceride levels are slightly reduced after 18 weeks of age
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• mice show increased C-reactive protein levels in the blood
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• mice develop glucose intolerance
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• liver insulin resistance is seen under basal conditions and is more pronounced under high-fat diet conditions
• high-fat diet induces insulin resistance to a greater extent than in controls
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• peri-pancreatic adipose tissue expresses high levels of IL-6, TNF-alpha and IL-1 beta at 7 weeks of age
• peri-pancreatic adipose tissue adipocytes show increased levels of IL-6, TNF-alpha and IL-1 beta
• however, pancreatic T cells and pancreatic macrophages exhibit cytokine levels similar to controls
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• circulating proinflammatory cytokines IL-6, TNF-alpha and IL-1 beta, but not IFN-gamma, are elevated before the onset of diabetes at 7 weeks of age
• mice exhibit increased systemic cytokines at 14 weeks of age or older
• high-fat diet augments cytokine production in peri-pancreatic adipose tissue and disruption of islets
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• the chemokine CCL5 is upregulated in pancreatic islets at 7 weeks of age before diabetes onset, while other chemokines such as CCL2, CCL21, CXCL19, and CXCL10, are weakly upregulated
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immune system
myocarditis
(
J:228009
)
|
• mice exhibit cardiac myocarditis at 14 weeks of age or older
|
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• accumulation of white blood cells invading into islets
• CD8+ T and CD4+ T cells infiltrate into the islets by 12 weeks of age
• MCHII+CD11b+CD11c- macrophages, CD3e+ T cells and CD19+ B cells are increased in the pancreases of mutants
• macrophage infiltration into the pancreas by 14 weeks of age and these macrophages express high levels of proinflammatory cytokines
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• mice show increased C-reactive protein levels in the blood
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• peri-pancreatic adipose tissue expresses high levels of IL-6, TNF-alpha and IL-1 beta at 7 weeks of age
• peri-pancreatic adipose tissue adipocytes show increased levels of IL-6, TNF-alpha and IL-1 beta
• however, pancreatic T cells and pancreatic macrophages exhibit cytokine levels similar to controls
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• circulating proinflammatory cytokines IL-6, TNF-alpha and IL-1 beta, but not IFN-gamma, are elevated before the onset of diabetes at 7 weeks of age
• mice exhibit increased systemic cytokines at 14 weeks of age or older
• high-fat diet augments cytokine production in peri-pancreatic adipose tissue and disruption of islets
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• the chemokine CCL5 is upregulated in pancreatic islets at 7 weeks of age before diabetes onset, while other chemokines such as CCL2, CCL21, CXCL19, and CXCL10, are weakly upregulated
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• Th1 (IFN-gamma+CD4+) and Th17 (IL-17+CD4+) effecter T-cell subsets are expanded while the regulatory T-cell subset (CD4+CD25+Foxp3+) is reduced in the pancreatic lymph nodes
• increase in activated dendritic cells in the lymph node of pancreases
• autoantigen NRP-V7-positive CD8+ T cells, targeting a peptide from islet-specific glucose-6-phosphatase catalytic subunit-related protein, are detected in the pancreatic lymph nodes and the spleen at 12 weeks of age
• prophylactic insulin therapy at the age of 5 weeks for 9 weeks partially ameliorates development of diabetes phenotypes including immune cells infiltration, beta-cell apoptosis and islet disruptions
• mice treated with intraperitoneal injection of NF-kappaB activation inhibitor II JSH-23 at 5 weeks of age ameliorates diabetes progression
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• mice have increased levels of insulin autoantibody in the blood
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| type 1 diabetes mellitus | DOID:9744 |
OMIM:222100 |
J:228009 | |
