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Phenotypes Associated with This Genotype
Genotype
MGI:5707775
Allelic
Composition
Senp1tm1Wami/Senp1tm1Wami
Tg(Fabp4-cre)#Abel/0
Genetic
Background
B6.Cg-Senp1tm1Wami Tg(Fabp4-cre)#Abel
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Senp1tm1Wami mutation (0 available); any Senp1 mutation (65 available)
Tg(Fabp4-cre)#Abel mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
adipose tissue
• 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
• 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
• reduction in fat pad weight at 14 weeks of age

behavior/neurological
• increase in water consumption
• however, food consumption is similar to controls

cardiovascular system
• mice exhibit cardiac myocarditis at 14 weeks of age or older

endocrine/exocrine glands
• structures of pancreatic islets are disrupted, with increased apoptosis of beta cells after onset of diabetes and more severe at later stages
• insulin secretion declines after 10 weeks of age
• glucose-stimulated insulin secretion from isolated islets is reduced
• 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

growth/size/body
• lower body weight after onset of diabetes

homeostasis/metabolism
• insulin secretion declines after 10 weeks of age
• glucose-stimulated insulin secretion from isolated islets is reduced
• age-dependent increase in glucose levels
• high-fat diet accelerates hyperglycemia with onset at 8 weeks of age
• 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
• mice show increased beta-hydroxybutyrate levels in the blood
• 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
• triglyceride levels are slightly reduced after 18 weeks of age
• mice show increased C-reactive protein levels in the blood
• mice develop glucose intolerance
• 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
• 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
• 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
• 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

immune system
• mice exhibit cardiac myocarditis at 14 weeks of age or older
• 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
• mice show increased C-reactive protein levels in the blood
• 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
• 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
• 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
• 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
• mice have increased levels of insulin autoantibody in the blood

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
type 1 diabetes mellitus DOID:9744 OMIM:222100
J:228009


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/19/2024
MGI 6.23
The Jackson Laboratory