Phenotypes associated with this allele

• Allele Symbol: C2cd5^{Gt(IST12020E4)Tigm}
• Allele Name: gene trap IST12020E4, Texas A&M Institute for Genomic Medicine
• Allele ID: MGI:4044687
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	C2cd5^Gt(IST12020E4)Tigm/C2cd5^Gt(IST12020E4)Tigm	C57BL/6N-C2cd5^Gt(IST12020E4)Tigm	MGI:6402053

Genotype
MGI:6402053

hm1

• Allelic Composition: C2cd5^{Gt(IST12020E4)Tigm}/C2cd5^{Gt(IST12020E4)Tigm}
• Genetic Background: C57BL/6N-C2cd5^{Gt(IST12020E4)Tigm}

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

growth/size/body

obese ( J:284780 )

• mice develop obesity under normal chow diet (NCD) or after feeding with an HFD (60kcal% fat) for 8 weeks

• however, food intake is normal under both NCD and HFD conditions

increased susceptibility to age related obesity ( J:284780 )

• mice exhibit higher body weight gain than wild-type controls under normal chow diet (NCD) conditions, esp. as they age

increased susceptibility to diet-induced obesity ( J:284780 )

• mice exhibit faster gain body weight than wild-type controls under a 60% high-fat diet (HFD)

• difference in body weight is mainly due to increased fat accumulation rather than lean body weight changes

homeostasis/metabolism

decreased fatty acid oxidation ( J:284780 )

• expression of genes related to mitochondrial fatty acid oxidation is significantly reduced in BAT

• NCD-fed mice show a significantly lower fatty acid oxidation rate than wild-type controls in BAT and skeletal muscle homogenates

impaired adaptive thermogenesis ( J:284780 )

• after long-term cold exposure (6 degrees Celsius for 20 h), subcutaneous inguinal white adipose tissue (iWAT) displays less browning and larger adipocytes with significantly less UCP1 protein expression in NCD-fed mice than in wild-type controls

• during long-term cold challenge, core body temperatures remain significantly lower than those in wild-type controls, esp. during the first 4 h of cold exposure

decreased circulating adrenaline level ( J:284780 )

• plasma adrenaline levels are significantly lower than in wild-type controls under NCD, HFD, or cold challenge (NCD plus 2 h cold exposure) conditions

decreased circulating free fatty acids level ( J:284780 )

• mice fed either NCD or HFD for 8 weeks exhibit significantly lower plasma free fatty acid levels than wild-type controls fed the same diet

decreased core body temperature ( J:284780 )

• mice have significantly lower core body temperatures than wild-type controls both before and after cold challenge at 4 degrees Celsius for 2 h

increased adrenaline level ( J:284780 )

• mice fed with HFD for 8 weeks or fed with NCD plus cold challenge for 2 h have significantly higher adrenaline levels in total lysates of adrenal glands than wild-type controls, likely due to reduced adrenaline release from the adrenal gland medulla

• however, protein expression of tyrosine hydroxylase (TH) in adrenal glands is normal, suggesting that the adrenaline synthesis pathway is unaffected

increased noradrenaline level ( J:284780 )

• after long-term (20 h) cold exposure, NCD-fed mice show significantly higher norepinephrine levels in iWAT than wild-type controls

decreased energy expenditure ( J:284780 )

• NCD-fed mice show significantly lower energy expenditure than wild-type controls during both dark and light periods

• HFD-fed mice show significantly reduced energy expenditure only during the light period

increased susceptibility to diet-induced obesity ( J:284780 )

• mice exhibit faster gain body weight than wild-type controls under a 60% high-fat diet (HFD)

• difference in body weight is mainly due to increased fat accumulation rather than lean body weight changes

decreased oxygen consumption ( J:284780 )

• NCD-fed mice show significantly lower oxygen consumption rates than wild-type controls during both dark and light periods

• HFD-fed mice show significantly lower oxygen consumption rates only during the light period

abnormal glucose homeostasis ( J:284780 )

• after HFD feeding for 6 weeks, mice require less glucose infusion to maintain euglycemia and average glucose infusion rate is significantly decreased during euglycemic clamps

• rate of glucose disappearance is significantly lower under both basal and clamp conditions

increased fasting circulating glucose level ( J:284780 )

• mice fed a HFD feeding for only 5 to 6 weeks show significantly higher fasting blood glucose levels than wild-type controls

impaired glucose tolerance ( J:284780 )

• after HFD feeding for only 5 to 6 weeks, mice show reduced glucose tolerance relative to wild-type controls

decreased hepatic glucose production ( J:284780 )

• basal hepatic glucose production (HGP) is significantly lower than that in wild-type controls

• insulin-induced suppression of HGP is significantly greater than that in wild-type controls

insulin resistance ( J:284780 )

• after HFD for only 5 to 6 weeks, mice show reduced insulin sensitivity relative to wild-type controls

increased liver triglyceride level ( J:284780 )

• mice fed either NCD or HFD have significantly higher liver triglyceride levels than wild-type controls fed the same diet

decreased basal metabolism ( J:284780 )

• mice exhibit much lower basal metabolic rates than wild-type controls during the light period

increased lipogenesis ( J:284780 )

• mice fed NCD show increased expression of the lipogenic genes Fasn (fatty acid synthase) and Pparg (peroxisome proliferator-activated receptor gamma) in white adipose tissue, suggesting activation of the lipogenesis pathway

impaired lipolysis ( J:284780 )

• mice fed with either NCD or an HFD for 10 weeks show significantly lower cAMP levels than wild-type controls in brown adipose tissue (BAT)

• mice with NCD plus cold challenge (CC) at 4 degrees Celsius for 2 h show significantly lower cAMP levels than wild-type controls in subcutaneous inguinal white adipose tissue (iWAT) and skeletal (gastrocnemius) muscle

• mice fed with either NCD or an HFD show significantly reduced phosphorylation of hormone-sensitive lipase (HSL) at Ser660 (a PKA phosphorylation site) and protein levels of ATGL (the first lipase in the lipolysis pathway) in BAT and in iWAT

• however, response to beta3-adrenoceptor agonist CL316243-induced phosphorylation of HSL at PKA site Ser660 and cAMP production in subcutaneous adipose tissue is normal

liver/biliary system

increased liver triglyceride level ( J:284780 )

• mice fed either NCD or HFD have significantly higher liver triglyceride levels than wild-type controls fed the same diet

hepatic steatosis ( J:284780 )

• mice exhibit significant accumulation of lipid droplets in the liver under both NCD and HFD conditions, as shown by Oil Red O staining

adipose tissue

increased brown fat cell lipid droplet size ( J:284780 )

• H&E staining indicates more and larger lipid droplets in BAT

increased brown fat lipid droplet number ( J:284780 )

• H&E staining indicates more and larger lipid droplets in BAT

increased white fat cell size ( J:284780 )

• white adipose tissue (WAT) adipocytes are significantly larger than those in wild-type control mice under both NCD and HFD conditions

decreased adipocyte glucose uptake ( J:284780 )

• after HFD feeding for 6 weeks, mice exhibit decreased insulin-stimulated glucose uptake into WAT but not brain during the euglycemic clamp

abnormal beige fat cell physiology ( J:284780 )

• after long-term (20 h) or short-term (2 h) cold exposure, gene expression of markers related to beige fat, mitochondrial thermogenesis, and fatty acid oxidation are significantly lower than in wild-type controls

• after long-term (20 h) cold exposure, UCP1 protein expression in beige fat is lower than that in wild-type controls

abnormal brown adipose tissue thermogenesis ( J:284780 )

• mice exhibit reduced thermogenesis with significantly less UCP1 protein expression in BAT

cellular

decreased adipocyte glucose uptake ( J:284780 )

• after HFD feeding for 6 weeks, mice exhibit decreased insulin-stimulated glucose uptake into WAT but not brain during the euglycemic clamp

decreased cardiac muscle cell glucose uptake ( J:284780 )

• after HFD feeding for 6 weeks, mice exhibit decreased insulin-stimulated glucose uptake into heart during the euglycemic clamp

decreased skeletal muscle cell glucose uptake ( J:284780 )

• after HFD feeding for 6 weeks, mice exhibit decreased insulin-stimulated glucose uptake into different skeletal muscles during the euglycemic clamp

• Akt phosphorylation at Ser473 is significantly reduced in gastrocnemius muscle, suggesting impaired insulin signaling in skeletal muscle

• tendency towards lower insulin-stimulated glucose transport activity in isolated soleus muscle

decreased fatty acid oxidation ( J:284780 )

• expression of genes related to mitochondrial fatty acid oxidation is significantly reduced in BAT

• NCD-fed mice show a significantly lower fatty acid oxidation rate than wild-type controls in BAT and skeletal muscle homogenates

endocrine/exocrine glands

abnormal adrenal gland secretion ( J:284780 )

• isolated adrenal glands exhibit a significant reduction in both basal and nicotine-induced adrenaline release relative to wild-type glands

muscle

decreased cardiac muscle cell glucose uptake ( J:284780 )

• after HFD feeding for 6 weeks, mice exhibit decreased insulin-stimulated glucose uptake into heart during the euglycemic clamp

decreased skeletal muscle cell glucose uptake ( J:284780 )

• after HFD feeding for 6 weeks, mice exhibit decreased insulin-stimulated glucose uptake into different skeletal muscles during the euglycemic clamp

• Akt phosphorylation at Ser473 is significantly reduced in gastrocnemius muscle, suggesting impaired insulin signaling in skeletal muscle

• tendency towards lower insulin-stimulated glucose transport activity in isolated soleus muscle

cardiovascular system

decreased cardiac muscle cell glucose uptake ( J:284780 )

• after HFD feeding for 6 weeks, mice exhibit decreased insulin-stimulated glucose uptake into heart during the euglycemic clamp

behavior/neurological

decreased vertical activity ( J:284780 )

• HFD-fed mice show significantly lower z-axis activity (rearing) than wild-type controls only during the dark period