Phenotypes associated with this allele

• Allele Symbol: Tg(Alb-SREBF1_ic)#Jkot
• Allele Name: transgene insertion, Jorg Kotzka
• Allele ID: MGI:6259431
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(Alb-SREBF1_ic)#Jkot/0	involves: C57BL/6	MGI:6259432

Genotype
MGI:6259432

tg1

• Allelic Composition: Tg(Alb-SREBF1_ic)#Jkot/0
• Genetic Background: involves: C57BL/6

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

mortality/aging

decreased survivor rate ( J:185313 )

• survival rate is reduced, with 17% of offspring dying within the first 3 days after delivery compared to 6% of offspring for controls

postnatal lethality, incomplete penetrance ( J:185313 )

• 17% of offspring die within the first 3 days after delivery compared to 6% of offspring for controls

cellular

abnormal cellular respiration ( J:249664 )

• hepatic beta-oxidation-linked maximal respiratory capacity is increased in 36 week old fasted mice

abnormal aerobic respiration ( J:249664 )

• hepatic tricarboxylic acid (TCA) cycle-linked respiration is increased in 36 week old fasted mice

• TCA cycle-linked respiration is increased in the gastrocnemius of fasted 18 week old mice but not 36 week old mice

• in the fed state, 36 week old mice show higher TCA cycle-linked respiration in the soleus muscle

abnormal lipid oxidation ( J:249664 )

• impaired lipid oxidation, with an inability to switch from glucose to lipid oxidation

growth/size/body

growth/size/body region phenotype ( J:249664 )

N • body weight is unchanged at 18 and 36 weeks of age

increased body fat mass ( J:185313 )

• total fat mass is increased more than 2-fold

increased lean body mass ( J:185313 )

decreased body weight ( J:185313 )

• weight of mice is about 10% lower than in controls at 6 weeks of age

increased susceptibility to weight gain ( J:185313 )

• weight of mice is about 10% lower than in controls at 6 weeks of age, however weight gain persists in mutants until 24 weeks to about twice that seen in controls

• at 24 weeks, total body weight is about 20% higher

• weight gain per MJ food intake is more than 2-fold compared to controls

enlarged liver ( J:185313 , J:249664 )

• mice exhibit enlarged livers at 24 weeks of age (J:185313)

• 36 week old mice exhibit large livers with 87% higher hepatic lipid levels (J:249664)

integument

increased subcutaneous adipose tissue amount ( J:249664 )

• subcutaneous fat depots are increased by 275%

behavior/neurological

decreased food intake ( J:185313 )

• mice consume 10% less food than controls and food intake by body weight is slightly reduced

adipose tissue

increased subcutaneous adipose tissue amount ( J:249664 )

• subcutaneous fat depots are increased by 275%

increased white adipose tissue amount ( J:249664 )

• visceral fat depots are increased by 225%

increased body fat mass ( J:185313 )

• total fat mass is increased more than 2-fold

abnormal fat pad morphology ( J:185313 )

• total increase of visceral fat depots, with visceral fat increased more than 3-fold either directly or in relation to body weight

• gluteo-femoral fat mass is greatly increased

• adipose depots show simple hyperplasia but no evidence of adipocyte hypertrophy or infiltrating macrophages

abnormal epididymal fat pad morphology ( J:185313 )

• the epididymal fat mass is greatly increased

abnormal inguinal fat pad morphology ( J:185313 )

• inguinal fat mass is greatly increased

homeostasis/metabolism

increased circulating glucose level ( J:185313 )

• blood glucose is nearly doubled

increased circulating insulin level ( J:185313 )

• insulin levels are increased about 4-fold

increased circulating leptin level ( J:185313 )

• leptin levels are elevated about 3-fold

increased circulating alanine transaminase level ( J:185313 )

• alanine aminotransferase (ALT) levels are nearly doubled

increased circulating aspartate transaminase level ( J:185313 )

• aspartate aminotransferase (AST) levels are nearly doubled

increased respiratory quotient ( J:249664 )

• mice exhibit high respiratory quotients during light versus dark phases, indicating impaired metabolic flexibility

insulin resistance ( J:185313 , J:249664 )

• the surrogate parameter for insulin resistance HOMA-IR is elevated about 3-fold and the surrogate parameter for insulin sensitivity QUICKI is reduced by 30% (J:185313)

• insulin-induced suppression of endogenous glucose production is 47% lower, indicating hepatic insulin resistance (J:249664)

• however, fasting blood glucose and insulin levels are unchanged in 18 week old mice (J:249664)

abnormal lipid homeostasis ( J:249664 )

• mice exhibit increased hepatic de novo lipogenesis

• mice show an increase in lipogenic gene expression in the liver and adipose tissue

abnormal lipid oxidation ( J:249664 )

• impaired lipid oxidation, with an inability to switch from glucose to lipid oxidation

decreased saturated fatty acids level ( J:185313 )

• content of saturated fatty acids in the liver is reduced 25% for stearic acid (C18:0), however there is no difference in palmitic acid (C16:0) content

decreased unsaturated fatty acids level ( J:185313 )

• the content of polyunsaturated fatty acid as linoleic acid (C18:2) or arachidonic acid (C20:4) is reduced by about 20% and 30%, respectively

increased fatty acids level ( J:185313 )

• total fatty acid levels in the liver are increased about 2-fold

• however, total fatty acid in adipose tissue is not altered

increased circulating free fatty acids level ( J:185313 )

• serum free fatty acids levels are increased about 2-fold

increased unsaturated fatty acids level ( J:185313 )

• content of monounsaturated fatty acids is increased about 3-fold for palmitoleic acid (C16:1) and increased 30% for oleic acid (C18:1)

• the content of polyunsaturated fatty acid as alpha-linolenic acid (C18:3) is increased about 30%

abnormal ceramide level ( J:249664 )

• C24:1 and C20:0 ceramides are increased in 18 weeks of liver

• C16, C20 and C24:1 ceramides are decreased in 36 weeks old liver

• however, ceramide levels are normal in muscle

increased triglyceride level ( J:185313 )

• triglyceride levels are increased 2-fold

• however, cholesterol levels are unaltered

abnormal lipid metabolism ( J:185313 )

• fatty acids desaturation indices are increased about 3-fold for C16:0 to C16:1 and about 2-fold for C18:0 to C18:1, the elongation index is decreased about 30%, and de novo lipid index is elevated about 20%

liver/biliary system

abnormal liver morphology ( J:185313 , J:249664 )

• fatty acid composition of the liver is altered with a shift to monosaturated fats (J:185313)

• several species of cytosolic diacylglycerol (C18:1/C16:0, C18:1/C18:1) containing at last one unsaturated fatty acid, gradually increase in the liver (J:249664)

enlarged liver ( J:185313 , J:249664 )

• mice exhibit enlarged livers at 24 weeks of age (J:185313)

• 36 week old mice exhibit large livers with 87% higher hepatic lipid levels (J:249664)

hepatic steatosis ( J:185313 , J:249664 )

• mice fed a standard diet show mild hepatic lipid accumulation at 24 weeks of age, with pale, enlarged livers and liver tissue being more dimorphous due to less dense cytoplasm with more vacuoles and showing higher accumulation of lipid droplets, located mainly around the nucleus and centered around the portal vein (J:185313)

• increase in hepatic lipid accumulation, with 36 week old mice showing 87% higher hepatic lipid levels (J:249664)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
metabolic dysfunction-associated steatotic liver disease		DOID:0080208	OMIM:613282 OMIM:613387	J:249664