Phenotypes Associated with This Genotype

Genotype
MGI:5437999

• Allelic Composition: Tg(Myl2-FGF19)1Dfre/?
• Genetic Background: involves: FVB

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

muscle

decreased skeletal muscle triglyceride level ( J:76323 )

• muscles of mutants have reduced triglyceride levels

growth/size/body

decreased body weight ( J:76323 )

• mutants weight less than controls when fed a standard chow diet, with a significant difference in weight for males at 5 days of age and at 31 days of age for females

decreased susceptibility to diet-induced obesity ( J:76323 )

• males and females are protected from high fat diet obesity, with fat pads weighting less than those from controls and exhibit lower leptin levels

adipose tissue

increased brown adipose tissue amount ( J:76323 )

• interscapular brown adipose tissue depot is enlarged, however it appears histologically normal

decreased total body fat amount ( J:76323 )

• reduction in fat content

decreased epididymal fat pad weight ( J:76323 )

♂

decreased retroperitoneal fat pad weight ( J:76323 )

behavior/neurological

increased food intake ( J:76323 )

• increase in total food intake

homeostasis/metabolism

decreased circulating glucose level ( J:76323 )

• when fed a high fat diet, mutant males exhibit lower glucose levels than controls in response to insulin injection

decreased circulating glucagon level ( J:76323 )

decreased circulating insulin level ( J:76323 )

• mutant males fed a high or low fat diet exhibit decreased insulin levels

decreased circulating insulin-like growth factor I level ( J:76323 )

decreased circulating leptin level ( J:76323 )

increased body temperature ( J:76323 )

• very small (about 0.2 C) increase in temperature as mutants approach the nadir of the diurnal rhythm

abnormal energy homeostasis ( J:76323 )

• metabolizable energy, measured as protein and fat intake, or as energy content, is greater than in wild-type mice

increased energy expenditure ( J:76323 )

• the increase in metabolizable energy with no increase in growth or fat storage and the increase in oxygen consumption with no change in respiratory quotient indicates an increase in energy expenditure

decreased susceptibility to diet-induced obesity ( J:76323 )

• males and females are protected from high fat diet obesity, with fat pads weighting less than those from controls and exhibit lower leptin levels

increased oxygen consumption ( J:76323 )

• both males and females exhibit a higher VO2, most prominent during the night when mice are active and feeding

improved glucose tolerance ( J:76323 )

• on a chow or a high fat diet, mutants exhibit improved glucose tolerance compared to controls on the same diet

increased insulin sensitivity ( J:76323 )

• increase in insulin sensitivity as indicated by the decrease in glucose excursion in the glucose tolerance test, the lower glucose levels in the insulin suppression test, and the lower insulin levels

decreased liver triglyceride level ( J:76323 )

• mutants fed either a low or a high fat diet have reduced liver triglyceride levels

decreased skeletal muscle triglyceride level ( J:76323 )

• muscles of mutants have reduced triglyceride levels

increased basal metabolism ( J:76323 )

• increase in oxygen consumption and increased body temperature without differences in activity indicate increased metabolic rate

increased incidence of tumors by chemical induction ( J:187236 )

• administration of diethylnitrosamine (DEN), a liver carcionogen, accelerates the development of hepatocellular carcinoma (HCC), such that aggressive HCC is seen by 4 months of age

liver/biliary system

increased hepatocyte proliferation ( J:77160 )

• by 2-4 months of age, pericentral hepatocytes exhibit increased cell proliferation; proliferation is higher in females than males

abnormal liver morphology ( J:76323 , J:77160 )

• mutants older then 5 months exhibit dysplastic changes in the liver (J:76323)

• mutants exhibit dysplastic changes in the liver by 7-9 months of age; 33% of females and 7% of males show hepatocellular dysplasia without neoplasia within this age range (J:77160)

• dysplastic foci are predominately of the small-cell type and oriented around central veins (J:77160)

decreased liver triglyceride level ( J:76323 )

• mutants fed either a low or a high fat diet have reduced liver triglyceride levels

increased liver tumor incidence ( J:77160 )

• 53% of mutants develop liver tumors by 10-12 months of age

increased hepatocellular carcinoma incidence ( J:77160 , J:187236 )

• 80% of females and 22% of males exhibit locally invasive hepatocellular carcinoma at 10-12 months of age (J:77160)

• tumors are solitary or multifocal, involving different liver lobes (J:77160)

• hepatocellular carcinomas are predominately the solid type although sometimes a trabecular pattern is seen (J:77160)

• tumors do not metastasize (J:77160)

cellular

increased hepatocyte proliferation ( J:77160 )

• by 2-4 months of age, pericentral hepatocytes exhibit increased cell proliferation; proliferation is higher in females than males

neoplasm

increased incidence of tumors by chemical induction ( J:187236 )

• administration of diethylnitrosamine (DEN), a liver carcionogen, accelerates the development of hepatocellular carcinoma (HCC), such that aggressive HCC is seen by 4 months of age

increased liver tumor incidence ( J:77160 )

• 53% of mutants develop liver tumors by 10-12 months of age

increased hepatocellular carcinoma incidence ( J:77160 , J:187236 )

• 80% of females and 22% of males exhibit locally invasive hepatocellular carcinoma at 10-12 months of age (J:77160)

• tumors are solitary or multifocal, involving different liver lobes (J:77160)

• hepatocellular carcinomas are predominately the solid type although sometimes a trabecular pattern is seen (J:77160)

• tumors do not metastasize (J:77160)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:77160 , J:187236