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Phenotypes Associated with This Genotype
Genotype
MGI:7314952
Allelic
Composition
Sdhbtm1c(EUCOMM)Hmgu/Sdhbtm1c(EUCOMM)Hmgu
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: C57BL/6J * C57BL/6N * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sdhbtm1c(EUCOMM)Hmgu mutation (0 available); any Sdhb mutation (29 available)
Tg(Ins2-cre)23Herr mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• young mice exhibit reduced insulin release following glucose administration
• islets fail to secrete insulin in response to leucine in 5-week-old mice
• islets show reduced glucose-stimulated first- and second-phase insulin secretion in 5-week-old mice
• exendin-4-augmented insulin secretion is slightly impaired in islets, while potassium chloride-induced insulin secretion is not altered, indicating an intact insulin secretion mechanism downstream of mitochondrial metabolism
• rapamycin treatment enhances insulin secretion under high glucose with no changes at resting glucose level
• mice show increased fasting glucose levels at 20 weeks of age
• mice show a progressive rise in fed glucose levels; while young mice are normoglycemic and normoinsulinemic until 6 weeks, hyperglycemia is evident by 10 weeks
• mice develop insulinopenic diabetes at pubertal age
• mice show low fasting serum insulin levels at 20 weeks of age
• young mice are mildly glucose intolerant with unchanged insulin sensitivity when challenged by intraperitoneal glucose tolerance test
• acute treatment with rapamycin marginally improves glucose intolerance

endocrine/exocrine glands
• by 20 weeks, but not at 5 weeks, islets exhibit large membraned vacuoles containing engulfed organelles, including insulin granules and damaged mitochondria
• mice show a progressive reduction in beta-cell mass without alterations in alpha-cell mass
• islets show nearly undetectable mitochondrial electron transport chain complex CII activity, elevated succinate levels, increase in protein lysine succinylation and increase in expression of the dessucinylation enzyme SIRT5
• islets show reduced basal and glucose-stimulated respiration and reduced maximal respiration and spare reserve capacity
• islets show a more than 50% reduction in ATP synthase-related oxygen consumption rate following oligomycin injection
• glucose-exposed islets fail to increase the ATP to ADP ratio
• islets show accumulation of succinate, with no change in fumarate levels, fatty acid intermediates, nucleic acid building blocks and precursors of protein synthesis despite a deficit of free amino acid pool
• homeostatic model assessment of beta-cell function as a percentage is reduced
• glucose-stimulated beta-cell replication is impaired in islets of prediabetic 5-week-old mice
• young mice exhibit reduced insulin release following glucose administration
• islets fail to secrete insulin in response to leucine in 5-week-old mice
• islets show reduced glucose-stimulated first- and second-phase insulin secretion in 5-week-old mice
• exendin-4-augmented insulin secretion is slightly impaired in islets, while potassium chloride-induced insulin secretion is not altered, indicating an intact insulin secretion mechanism downstream of mitochondrial metabolism
• rapamycin treatment enhances insulin secretion under high glucose with no changes at resting glucose level

cellular
• islets show reduced basal and glucose-stimulated respiration and reduced maximal respiration and spare reserve capacity
• islets show nearly undetectable mitochondrial electron transport chain complex CII activity, elevated succinate levels, increase in protein lysine succinylation and increase in expression of the dessucinylation enzyme SIRT5


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
12/10/2024
MGI 6.24
The Jackson Laboratory