Phenotypes associated with this allele

• Allele Symbol: Nadk2^{tm1a(EUCOMM)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4842252
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nadk2^tm1a(EUCOMM)Wtsi/Nadk2^tm1a(EUCOMM)Wtsi	involves: C57BL/6N * C57BL/6NTac	MGI:6116209

Genotype
MGI:6116209

hm1

• Allelic Composition: Nadk2^{tm1a(EUCOMM)Wtsi}/Nadk2^{tm1a(EUCOMM)Wtsi}
• Genetic Background: involves: C57BL/6N * C57BL/6NTac
• Cell Lines: EPD0638_1_A06

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

liver/biliary system

enlarged liver ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet

increased liver triglyceride level ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet, mice display massive TG accumulation in the liver

• after a 24-hour fasting, hepatic TG levels are significantly higher than those in wild-type livers

hepatic steatosis ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet, mice display enlarged pale livers; however, body weights and fat composition remain normal

• AHF diet-induced hepatic steatosis is partly due to increased ROS levels and reduced activities of the key hepatic regulators in FAO and lipolysis, including CREB3L3 (CREBH) and PPARA

liver degeneration ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet, livers show a tendency for elevated hepatocyte ballooning

liver fibrosis ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet, livers show a tendency for elevated fibrosis

pale liver ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet

abnormal liver physiology ( J:255700 )

• on a normal chow diet, hepatic levels of mitochondrial NADP(H) are significantly lower than those in wild-type controls; however, hepatic levels of cytosolic NADP(H) remain normal

• on an atherogenic high-fat (AHF) diet, hepatic NAD levels and the activity of mitochondrial sirtuins are significantly lower than those in wild-type controls

homeostasis/metabolism

decreased fatty acid oxidation ( J:255700 )

• after glucagon treatment, primary hepatocytes from mutant mice fail to show an increase in fatty acid oxidation (FAO), unlike wild-type hepatocytes

• during fasting, mice show a severely reduced level of FAO relative to wild-type controls; however, no differences are noted when mice are fed ad libitum

increased circulating carnitine level ( J:255700 )

• serum levels of C10:2 carnitine are doubled relative to wild-type controls

• serum levels of other acylcarnitine species, including C4-OH, C14-OH, C16:1, and C18:2 acylcarnitines, are also significantly increased relative to wild-type controls

increased lysine level ( J:255700 )

• hepatic levels of lysine and N-alpha-acetyl-lysine are increased ~4-fold and 7-fold, respectively, relative to wild-type controls

increased circulating lysine level ( J:255700 )

• serum levels of lysine are increased by >3-fold relative to wild-type controls

• serum levels of D- and L- enantiomers of lysine (DL-lysine) are increased by 7-fold

increased circulating free fatty acids level ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet, serum free fatty acid (FFA) levels are significantly higher than those in control mice

• after a 24-hour fasting, serum FFA levels are significantly higher than those in control mice, consistent with impaired fasting-induced fatty acid oxidation

increased circulating triglyceride level ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet, serum TG levels are significantly higher than those in control mice

decreased energy expenditure ( J:255700 )

• during fasting, mice show a modest reduction in energy expenditure relative to wild-type controls; however, locomotor activity remains normal

increased respiratory quotient ( J:255700 )

• at 1 hour after fasting, mice show a significant increase in RER relative to wild-type controls

increased liver triglyceride level ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet, mice display massive TG accumulation in the liver

• after a 24-hour fasting, hepatic TG levels are significantly higher than those in wild-type livers

cellular

decreased fatty acid oxidation ( J:255700 )

• after glucagon treatment, primary hepatocytes from mutant mice fail to show an increase in fatty acid oxidation (FAO), unlike wild-type hepatocytes

• during fasting, mice show a severely reduced level of FAO relative to wild-type controls; however, no differences are noted when mice are fed ad libitum

oxidative stress ( J:255700 )

• on a normal chow diet, the GSSG:GSH ratio (oxidized vs reduced glutathione), a marker for oxidative stress, is significantly increased in liver

• on an AHF diet, liver shows a dramatic increase in reactive oxygen species (ROS) levels relative to AHF-fed wild-type controls, as shown by dihydroethidium staining; however, no differences are noted on a normal chow diet

• PBS-treated primary hepatocytes isolated from adult mutant mice show a mild but significant increase in ROS levels relative to PBS-treated wild-type hepatocytes

• palmitic acid (PA)-treated primary hepatocytes show a ~3-fold increase in ROS levels relative to PA-treated wild-type hepatocytes

growth/size/body

enlarged liver ( J:255700 )

• after 3 weeks on an atherogenic high-fat (AHF) diet