Phenotypes Associated with This Genotype

Genotype
MGI:5694491

• Allelic Composition: Lrp6^tm1Arma/Lrp6^tm1Arma
• Genetic Background: C57BL/6-Lrp6^tm1Arma

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

homeostasis/metabolism

increased circulating bilirubin level ( J:210538 )

• mice on a high-cholesterol diet for 6 months exhibit elevated plasma levels of bilirubin

increased circulating aspartate transaminase level ( J:210538 )

• mice on a high-cholesterol diet for 6 months exhibit elevated plasma levels of aspartate aminotransferase

insulin resistance ( J:210538 )

• mice exhibit impaired response to intraperitoneal insulin administration

• however, mice have normal baseline insulin and glucose levels

abnormal lipid homeostasis ( J:210538 )

• mice on a high-cholesterol diet for 6 months exhibit greater neutral lipid storage in primary hepatocytes than wild-type hepatocytes

• mice fed a chow diet show increased hepatic triglyceride and VLDL particle synthesis and secretion

• mice on a high-cholesterol diet exhibit an increase in de novo lipogenesis

• however, mice show normal VLDL clearance

increased circulating triglyceride level ( J:210538 )

• mice on a high-cholesterol diet for 6 months show a 2-fold increase in plasma triglyceride levels, with a higher triglyceride in the VLDL fraction and higher cholesterol in the non-HDL cholesterol fraction

increased circulating VLDL triglyceride level ( J:210538 )

• the increase in triglyceride levels is predominantly associated with VLDL particles

• mice on a high-cholesterol diet for 6 months show higher triglyceride in the VLDL fraction

hyperlipidemia ( J:210538 )

increased cholesterol level ( J:210538 )

• chow fed mice show increased total cholesterol levels

• mice exhibit an increase in non-HDL cholesterol (IDL/LDL)

• mice on a high-cholesterol diet for 6 months show a 3-fold increase in total cholesterol levels compared to wild-type mice on the same diet

increased circulating LDL cholesterol level ( J:210538 )

• chow fed mice show increased LDL cholesterol

• mice on a high-cholesterol diet for 6 months show a 3-fold increase in total cholesterol levels and LDL cholesterol

increased liver cholesterol level ( J:210538 , J:225450 )

• mice on a high-cholesterol diet for 6 months exhibit higher hepatic cholesterol ester content (J:210538)

• mice fed a high cholesterol diet for 7 months show a greater hepatic fat content than wild-type mice (J:225450)

abnormal fatty acids level ( J:210538 )

• mice show greater 18:1n9 fatty acid content when fed a high-cholesterol diet compared to wild-type mice

increased liver triglyceride level ( J:210538 )

• mice on a high-cholesterol diet for 6 months exhibit higher total hepatic triglyceride content

immune system

liver inflammation ( J:225450 )

• mice on a chow diet exhibit infiltration of the liver with inflammatory cells at 9 months of age

• mice fed a high cholesterol diet for 7 months exhibit considerable infiltration of inflammatory cells into the liver that is not seen in wild-type mice fed the same diet

liver/biliary system

liver inflammation ( J:225450 )

• mice on a chow diet exhibit infiltration of the liver with inflammatory cells at 9 months of age

• mice fed a high cholesterol diet for 7 months exhibit considerable infiltration of inflammatory cells into the liver that is not seen in wild-type mice fed the same diet

abnormal liver morphology ( J:225450 )

• mice fed a high cholesterol diet exhibit altered hepatic tissues surrounding portal and central veins

enlarged liver ( J:210538 )

• mice on a high-cholesterol diet for 6 months exhibit gross enlargement of the liver

increased liver cholesterol level ( J:210538 , J:225450 )

• mice on a high-cholesterol diet for 6 months exhibit higher hepatic cholesterol ester content (J:210538)

• mice fed a high cholesterol diet for 7 months show a greater hepatic fat content than wild-type mice (J:225450)

increased liver triglyceride level ( J:210538 )

• mice on a high-cholesterol diet for 6 months exhibit higher total hepatic triglyceride content

hepatic steatosis ( J:210538 , J:225450 )

• mice on a high-cholesterol diet for 6 months develop fatty liver with higher fat content than in wild-type mice (J:210538)

• mice fed a high cholesterol diet for 7 months show a greater hepatic fat content than wild-type mice indicating development of hepatosteatosis (J:225450)

liver fibrosis ( J:225450 )

• mice fed a high cholesterol diet for 7 months develop liver fibrosis

growth/size/body

enlarged liver ( J:210538 )

• mice on a high-cholesterol diet for 6 months exhibit gross enlargement of the liver

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
steatotic liver disease		DOID:9452	OMIM:228100	J:225450