Phenotypes associated with this allele

• Allele Symbol: Ces1g^tm1Reli
• Allele Name: targeted mutation 1, Richard Lehner
• Allele ID: MGI:6164718
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ces1g^tm1Reli/Ces1g^tm1Reli	involves: 129S/SvEv * C57BL/6	MGI:6191761

Genotype
MGI:6191761

hm1

• Allelic Composition: Ces1g^tm1Reli/Ces1g^tm1Reli
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

growth/size/body

increased body weight ( J:262803 )

• at 24 weeks of age, mice fed a low-fat chow diet weighed significantly more than wild-type controls

obese ( J:262803 )

• mice fed a low-fat chow diet developed obesity

• dietary fish oil supplementation reversed the obese phenotype

increased susceptibility to weight gain ( J:262803 )

• starting at ~15 weeks of age, mice fed a low-fat chow diet gained more weight than wild-type controls; however, food intake per day was normal

• dietary fish oil supplementation completely prevented weight gain, resulting in body weights comparable to those of wild-type controls at the end of the 4-month diet intervention

homeostasis/metabolism

impaired adaptive thermogenesis ( J:262803 )

• in a cold tolerance test, mice showed reduced thermogenesis with decreased expression of uncoupling protein 1 (UCP-1) after cold exposure relative to wild-type controls

decreased energy expenditure ( J:262803 )

• mice showed decreased O₂ consumption and CO₂ production, suggesting a net overall reduction in energy expenditure

decreased carbon dioxide production ( J:262803 )

• mice showed decreased CO₂ production relative to wild-type controls

decreased oxygen consumption ( J:262803 )

• mice showed decreased O₂ consumption relative to wild-type controls

decreased respiratory quotient ( J:262803 )

• mice showed a decrease in the respiratory quotient (RQ) during the last period of the dark cycle (i.e., increased utilization of fatty acids)

increased respiratory quotient ( J:262803 )

• mice showed an increase in the respiratory quotient (RQ) during the first period of the dark cycle (i.e., increased glucose utilization)

abnormal glucose homeostasis ( J:262803 )

• mice showed impaired insulin tolerance in skeletal muscle and adipose tissue but not in the liver

decreased fasting circulating glucose level ( J:262803 )

• mice showed lower fasting concentration of glucose relative to wild-type controls

• fish oil supplementation had no effect on blood glucose disposal

increased circulating insulin level ( J:262803 )

• mice showed higher plasma insulin concentration relative to wild-type controls

increased insulin sensitivity ( J:262803 )

• in response to insulin challenge, phosphorylation of AKT (a downstream messenger in insulin signaling) was significantly increased in the liver

• however, phosphorylation of AKT was significantly decreased in skeletal muscle and adipose tissue

insulin resistance ( J:262803 )

• mice showed insensitivity to insulin

abnormal lipid homeostasis ( J:262803 )

• at 24 weeks of age, mice showed increased hepatic lipogenic gene and protein expression relative to wild-type controls

• in the fasted state, hepatic levels of active SREBP-1c (a master lipogenic transcription factor) in the nucleus were significantly higher than those in wild-type controls

• following incubation with oleic acid (OA), primary hepatocytes isolated from fasted mice showed increased de novo lipogenesis with an increased number of lipid droplets and higher lipid (TG) mass but similar incorporation of OA into different lipid species relative to wild-type hepatocytes

• incubation of hepatocytes with EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) reversed the increased lipogenic phenotype; the anti-lipogenic effect was mediated by lower nuclear SREBP-1c upon PUFA (polyunsaturated fatty acids) treatment

increased circulating cholesterol level ( J:262803 )

• increased plasma free cholesterol (FC) and cholesteryl ester (CE) levels in fasted mice at 5 months of age

increased circulating VLDL cholesterol level ( J:262803 )

• fasted mice showed increased plasma VLDL-cholesterol levels

increased circulating free fatty acids level ( J:262803 )

• increased plasma non-esterified fatty acid (NEFA) levels in fasted mice at 5 months of age

increased circulating phospholipid level ( J:262803 )

• increased plasma phospholipid (PL) levels in in fasted mice at 5 months of age

increased circulating triglyceride level ( J:262803 )

• increased plasma triglyceride (TG) levels in fasted mice at 5 months of age

increased circulating VLDL triglyceride level ( J:262803 )

• fasted mice showed increased plasma VLDL-TG levels

• in vivo VLDL secretion (measured following injection of P-407) was increased relative to wild-type controls

• increased VLDL-TG secretion was confirmed in isolated hepatocytes

• dietary fish oil supplementation normalized VLDL-TG secretion

hyperlipidemia ( J:262803 )

• at 5 months of age, fasted mice displayed increased plasma lipid (TG, FC, CE, PL, and NEFA) concentrations; plasma lipid levels were slightly higher in females compared to males

• dietary fish oil supplementation restored plasma TG, PL, and FC concentrations to wild-type levels

increased liver cholesterol level ( J:262803 )

• at 5 months of age, hepatic free cholesterol and cholesteryl ester levels were 150% and 250% higher, respectively, than those in wild-type controls

decreased saturated fatty acids level ( J:262803 )

• hepatocytes from chow diet-fed mice showed decreased concentration of saturated stearic acid in TG relative to wild-type hepatocytes

increased unsaturated fatty acids level ( J:262803 )

• hepatocytes from chow diet-fed mice accumulated significantly more EPA and DHA in TG in addition to palmitoleic acid relative to wild-type hepatocytes

• following dietary fish oil supplementation, mice showed increased accumulation of DHA in hepatic TG, with no differences observed in any other any other fatty acids or in other lipid species

increased liver triglyceride level ( J:262803 )

• at 5 months of age, hepatic triglyceride content was 300% higher than that in wild-type controls

abnormal apolipoprotein level ( J:262803 )

• mice showed increased secretion of newly synthesized apoB100 and apoB48 relative to wild-type controls, typical of VLDL over-secretion in vivo

• increased apoB100 and apoB48 secretion was confirmed in isolated hepatocytes

• dietary fish oil supplementation normalized both apoB100 and apoB48 secretions

abnormal circulating apolipoprotein level ( J:262803 )

• fasted mice showed increased plasma apoCIII levels and decreased apoCII levels relative to wild-type controls

abnormal circulating apolipoprotein E level ( J:262803 )

• fasted mice showed increased plasma apoE levels relative to wild-type controls

adipose tissue

abnormal brown adipose tissue morphology ( J:262803 )

• mice showed increased lipid storage in BAT relative to wild-type controls

decreased brown adipose tissue mass ( J:262803 )

• mice exhibited a trend for reduced brown adipose tissue (BAT) mass relative to wild-type controls

increased white fat cell size ( J:262803 )

• at 24 weeks of age, H&E staining of epididymal WAT revealed larger white adipocytes

increased white adipose tissue mass ( J:262803 )

• at 24 weeks of age, increased body weight was concomitant with an increase in WAT weight

liver/biliary system

increased liver cholesterol level ( J:262803 )

• at 5 months of age, hepatic free cholesterol and cholesteryl ester levels were 150% and 250% higher, respectively, than those in wild-type controls

increased liver triglyceride level ( J:262803 )

• at 5 months of age, hepatic triglyceride content was 300% higher than that in wild-type controls

hepatic steatosis ( J:262803 )

• fasted mice exhibited mild hepatic steatosis with no signs of acute or chronic liver inflammation

• dietary fish oil supplementation completely abolished the steatosis observed in livers from fasted mice fed standard chow

liver degeneration ( J:262803 )

• mice showed a modest increase in plasma alanine aminotransferase (AST) and plasma alanine aminotransferase (ALT) activity, indicating mild liver damage

• dietary fish oil supplementation normalized the activity of the hepatic enzymes AST and ALT in plasma

abnormal hepatocyte physiology ( J:262803 )

• isolated mutant hepatocytes showed increased VLDL-TG, apoB100 and apoB48 secretion relative to wild-type hepatocytes

behavior/neurological

hyperactivity ( J:262803 )

• mice showed increased total physical activity during the dark cycle