Phenotypes Associated with This Genotype

Genotype
MGI:3721145

• Allelic Composition: Prkci^tm1Rfar/Prkci⁺; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

increased circulating leptin level ( J:123964 )

abnormal circulating lipid level ( J:123964 )

• males and females have more serum lipid than wild-type mice

decreased circulating HDL cholesterol level ( J:123964 )

increased circulating cholesterol level ( J:123964 )

increased circulating LDL cholesterol level ( J:123964 )

increased circulating free fatty acids level ( J:123964 )

• serum free fatty acid levels are increased by 90% relative to wild-type mice

increased circulating triglyceride level ( J:123964 )

• fasting triglyceride levels are increased relative to in wild-type mice

abnormal glucose homeostasis ( J:123964 )

• in a euglycemic clamp assay, mice require a reduced rate of glucose infusion compared to wild-type mice to maintain euglycemia

increased circulating glucose level ( J:123964 )

• in mice fed ad libitum, serum glucose levels are increased

• fasting glucose levels during insulin and glucose tolerance tests is increased by 20% to 25%

• when dietary fat content is increased from 5% to 10% for 2 months, mice exhibit higher glucose levels than in wild-type mice at all time points and during fasting glucose tolerance testing

increased circulating insulin level ( J:123964 )

• in mice fed ad libitum, serum insulin levels are increased

impaired glucose tolerance ( J:123964 )

• in mice fed ad libitum, glucose tolerance impairment is comparable to or more severe than in homozygotes

insulin resistance ( J:123964 )

• in mice fed ad libitum, insulin tolerance is impairment is comparable to or more severe than in homozygotes

• in a euglycemic clamp assay, whole-body insulin resistance is accounted for by decreases in insulin-stimulated whole-body glucose uptake and muscle glucose uptake of 25% and 30%, respectively

cardiovascular system

decreased cardiac muscle cell glucose uptake ( J:123964 )

muscle

decreased muscle cell glucose uptake ( J:123964 )

• insulin-stimulated uptake of glucose and [³H]2-deoxyglucose in vastus laterallis, soleus and extensor digitorum longus, and heart muscles is reduced by 50% to 60% compared to in wild-type mice

decreased cardiac muscle cell glucose uptake ( J:123964 )

decreased skeletal muscle cell glucose uptake ( J:123964 )

liver/biliary system

hepatic steatosis ( J:123964 )

• even on a low-fat diet, hepatostetosis occurs and is more pronounced in heterogyzotes than in homozygotes

adipose tissue

decreased adipocyte glucose uptake ( J:123964 )

• insulin-stimulated glucose transport is impaired

growth/size/body

increased body weight ( J:123964 )

• body weight is increased relative to wild-type mice and homozygous mice

obese ( J:123964 )

• mice develop an obesity/diabetes syndrome associated with increased food intake

behavior/neurological

increased food intake ( J:123964 )

• mice consume 20% more regular chow than wild-type mice

immune system

increased susceptibility to autoimmune diabetes ( J:123964 )

• mice develop an obesity/diabetes syndrome associated with increased food intake

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:123964 )

cellular

decreased adipocyte glucose uptake ( J:123964 )

• insulin-stimulated glucose transport is impaired

decreased muscle cell glucose uptake ( J:123964 )

• insulin-stimulated uptake of glucose and [³H]2-deoxyglucose in vastus laterallis, soleus and extensor digitorum longus, and heart muscles is reduced by 50% to 60% compared to in wild-type mice

decreased cardiac muscle cell glucose uptake ( J:123964 )

decreased skeletal muscle cell glucose uptake ( J:123964 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome		DOID:0060611	OMIM:PS605552	J:123964
obesity		DOID:9970	OMIM:601665	J:123964
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:123964