Mouse Genome Informatics
cx1
    Fgfr4tm1Cxd/Fgfr4tm1Cxd
Tg(Myl2-FGF19)1Dfre/0

involves: 129S6/SvEvTac * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• the hepatocarcinogenesis observed in diethylnitrosamine (DEN) treated single Tg(Myl2-FGF19)1Dfre mutants is abolished in double mutants
• mutants do not develop gross or histological evidence of hepatocellular neoplasia unlike single Tg(Myl2-FGF19)1Dfre mutant mice which develop hepatocellular carcinoma
• the preneoplastic hepatocellular proliferation that is seen in single Tg(Myl2-FGF19)1Dfre mutants is not evident in double mutants

homeostasis/metabolism
• the hepatocarcinogenesis observed in diethylnitrosamine (DEN) treated single Tg(Myl2-FGF19)1Dfre mutants is abolished in double mutants


Mouse Genome Informatics
tg2
    Tg(Myl2-FGF19)1Dfre/?
involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• reduction in fat content
• 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
• 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
• interscapular brown adipose tissue depot is enlarged, however it appears histologically normal
• reduction in fat content

behavior/neurological
• increase in total food intake

homeostasis/metabolism
• when fed a high fat diet, mutant males exhibit lower glucose levels than controls in response to insulin injection
• mutant males fed a high or low fat diet exhibit decreased insulin levels
• very small (about 0.2 C) increase in temperature as mutants approach the nadir of the diurnal rhythm
• metabolizable energy, measured as protein and fat intake, or as energy content, is greater than in wild-type mice
• 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
• males and females are protected from high fat diet obesity, with fat pads weighting less than those from controls and exhibit lower leptin levels
• both males and females exhibit a higher VO2, most prominent during the night when mice are active and feeding
• on a chow or a high fat diet, mutants exhibit improved glucose tolerance compared to controls on the same diet
• 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
• muscles of mutants have reduced triglyceride levels
• mutants fed either a low or a high fat diet have reduced liver triglyceride levels
• increase in oxygen consumption and increased body temperature without differences in activity indicate increased metabolic rate
• 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
• by 2-4 months of age, pericentral hepatocytes exhibit increased cell proliferation; proliferation is higher in females than males
• 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)
• mutants fed either a low or a high fat diet have reduced liver triglyceride levels

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

tumorigenesis
• 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
• 53% of mutants develop liver tumors by 10-12 months of age
• 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
OMIM IDRef(s)
Hepatocellular Carcinoma 114550 J:77160 , J:187236