Mouse Genome Informatics
hm1
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/Gtf2ird1Tg(Alb1-Myc)166.8Sst
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• periorbital fullness is a characteristic of these mice
• 20% of mice have a misaligned jaw resulting in chronic overgrowth of teeth
• 20% of mice have a twisted snout
• in these severely affected mice, the snout is twisted to the left or right by 7 to 12 degrees
• mice have a characteristically short snout

growth/size
• 20% of mice have a twisted snout
• in these severely affected mice, the snout is twisted to the left or right by 7 to 12 degrees
• mice have a characteristically short snout
• body weight of 1- and 2- month old mice that have properly aligned jaws is a few grams less than controls
• weights of mice with misaligned jaws is dramatically less

skeleton
• periorbital fullness is a characteristic of these mice
• 20% of mice have a misaligned jaw resulting in chronic overgrowth of teeth

behavior/neurological
• the 20% of mice with malocclusions are unable to manipulate hard food pellets
• mice display an abnormal clasping or kicking behavior upon lifting

vision/eye
• periorbital fullness is a characteristic of these mice

Mouse Models of Human Disease
OMIM IDRef(s)
Williams-Beuren Syndrome; WBS 194050 J:102709


Mouse Genome Informatics
hm2
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/Gtf2ird1Tg(Alb1-Myc)166.8Sst
involves: C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants exhibit decreased circadian activity (less activity during the dark phase); females however, are more active than males
• mutants show a longer latency to eat than wild-type mice (hyponeophagia)
• mutants exhibit a longer latency to enter either the light or the dark compartment when beginning the experiment in the dark or light side of the light/dark box, respectively
• mutants display longer immobility and higher % immobility time before the first transition in the light/dark box test
• females are less immobile starting at the light side and more immobile starting at the dark side compared to males
• distance traveled in the light/dark box test is decreased; females are more active in the test than males
• mutants exhibit increased anxiety in all experimental settings
• in the elevated plus maze, females show fewer entries to the open arms, spend less time in the open arms, show decreased number of closed arm entries, decrease in the number and time of head dips, increased grooming time, and an increase in the number and time of stretched approaches in the closed arms
• males do not show abnormalities in the classical measures of anxiety on the elevated plus maze (time and entries into open arms), however, they show fewer head dips and more stretched approaches and longer grooming times, signs of anxiety
• mutants exhibit decreased locomotor activity with increased immobility during the first 5 min of the open field test and decreased immobility during the last 5 min of the session, indicating increased anxiety
• mutants exhibit decreased velocity and decreased number of rearings in a novel environment
• mutant males exhibit an elevated temperature increase 10 minutes after an initial stressor, indicating stress-induced hyperthermia (J:190478)
• mutants exhibit increased grooming time during the elevated plus maze test
• mutants spend longer time self-grooming during a 5 minute test compared to controls, indicating stress-induced grooming
• mutants exhibit decreased motor coordination on all three days of training on the rotarod; females show better motor coordination than males
• mutants show a shorter latency to fall from an inverted screen compared to controls, showing less strength and coordination
• mutants show decreased weight lifting ability, unable to lift the same amount of weight as controls
• males, but not females, show impaired strength in the horizontal bar test
• mutants exhibit decreased number of rearings in a novel environment
• males exhibit gait abnormalities such as increased variability in step patterns (increased % of single paw support, decreased % of diagonal support, decreased step sequence for alternate and increased for rotary patterns, and increased variability for coupling and phase dispersion), despite normal gait speed, stride length, cadence, and regularity (J:190478)
• hindpaws of males show decreased contact area, print area, stand index, intensity, print length, print width, and duty cycle (J:190478)
• mutants are impaired in nest building, leaving up to 50% of the nesting material intact, indicating impaired fine motor skills
• nest building is improved by providing shredded nesting material

growth/size
• analyzed only in males (J:190478)
• analyzed only in males (J:190478)

homeostasis/metabolism
• mutant males exhibit an elevated temperature increase 10 minutes after an initial stressor, indicating stress-induced hyperthermia (J:190478)
• stressed males exhibit elevated levels of corticosterone compared to wild-type mice, however no differences in corticosterone levels are seen in non-stressed males (J:190478)

craniofacial
• periorbital fullness
• about 20% of mutants exhibit a misaligned jaw

skeleton
• periorbital fullness
• about 20% of mutants exhibit a misaligned jaw

vision/eye
• periorbital fullness

Mouse Models of Human Disease
OMIM IDRef(s)
Williams-Beuren Syndrome; WBS 194050 J:190478


Mouse Genome Informatics
ht3
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/Gtf2ird1+
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• the first dysplastic hepatocytes are detected at 4 months of age but severe and wide-spread dysplasia only appear in males older than 1 year of age
• through the first year of life, liver weight to body weight ratios are 1.3 to 1.5 times higher than the ratio in wild-type mice
• as neoplastic lesions develop in mice, the liver weight/body weight ratio increases significantly reaching values 2.5 times higher than controls at 16 months of age

tumorigenesis
• mutants develop diffuse liver dysplasia by 6-9 months of age
• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a slightly higher incidence
• malignant neoplastic lesions appear between the 10 and 14 months of age, with 67% of males and 10% of females having carcinomas by 20 months of age (J:34434)
• the average tumor size in males is 1.0 x 1.4 cm (J:34434)
• these malignant lesions vary from well differentiated to poorly differentiated with the latter associated with intense mitotic activity, proliferation of neocapillaries, and large areas of hemorrhagic necrosis (J:34434)
• in late stage lesions, small ductular-like cells are found (J:34434)
• 23% of mutants develop hepatocellular carcinoma by 12 months of age (J:101128)


Mouse Genome Informatics
ht4
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/Gtf2ird1+
involves: C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants exhibit decreased circadian activity (less activity during the dark phase)
• mutants show a longer latency to eat than wild-type mice (hyponeophagia)
• mutants exhibit decreased motor coordination on the rotarod

growth/size
• analyzed only in males (J:190478)
• analyzed only in males (J:190478)


Mouse Genome Informatics
cx5
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/Gtf2ird1+
Tg(Alb-E2F1)8Sst/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants develop diffuse liver dysplasia by 3 months of age
• 22% of mutants develop hepatocellular carcinomas by 6 months of age and by 9 months of age, 100% of mutants show hepatocellular carcinomas, indicating that tumors are more severe and arise faster than in single transgenic mice
• tumors are predominantly moderately well differentiated with trabecular, solid and trabecular/pseudoglandular pattern

Mouse Models of Human Disease
OMIM IDRef(s)
Hepatocellular Carcinoma 114550 J:101128 , J:170790


Mouse Genome Informatics
cx6
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/0
Tg(MtTGFA)42Lmb/0

involves: C57BL/6 * CBA * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• three weeks after zinc administration through drinking water, the first signs of hepatic neoplasia are evident with large hepatocytes with compact nuclei being found around blood vessels
• after six weeks of zinc administration, 80% of mice display these neoplastic lesions
• after ten weeks of zinc administration, foci of dysplastic cells are found throughout the liver nodule
• intravascular spread of tumor cells is also observed ten weeks after zinc administration
• after 16 weeks of zinc administration, over 70% of mice carry single or multifocal nodules of which one quarter consist of well differentiated hepatocellular carcinomas displaying pseudoglandular or trabecular pattern
• the appearance of preneoplastic and neoplastic lesions also occur in mice with a delay of 6 to 8 weeks in mice not receiving zinc treatment


Mouse Genome Informatics
cx7
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/Gtf2ird1+
Tg(MtTGFA)42Lmb/0

involves: C57BL/6 * CBA * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice
• most mice by 2 months of age have extensive dysplastic changes in the liver ranging from moderate cellular pleomorphism and hypertrophy to more advanced poly morphisms with severe cytomegaly and karyomegaly
• hepatocytes often display abnormal nuclear structures (tripolar mitosis, chromosome bridges, aberrant chromosomal migration, intranuclear lipid droplets, and nuclear eosinophilic pseudoinclusions)
• these dysplastic changes started in the perivascular areas of the liver, are most advanced around the central veins and are spreading throughout the hepatic lobe
• metastasis to the lung and spleen is observed only rarely
• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins
• the liver weight/body weight ratio of young mice is significantly higher than controls
• after 4 months of age when large tumor masses are present in the liver, this ratio becomes much larger
• in mice that survive to 12 months of age, liver weight represents nearly 20% of body weight due to invasion of liver tumors into the abdominal cavity
• focal coagulative necrosis of hepatocyte groups with granulocytic reaction is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

tumorigenesis
• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence
• malignant neoplastic lesions appear between the 3 and 4 months of age, with 100% of males and 30% of females having carcinomas by 8 months of age
• the average tumor size for male mice is 1.9 x 1.9 cm and for female mice (0.6 x 1.1 cm)
• most malignant lesions display a trabecular histological pattern but solid or pseudoglandular types are also detectable
• these malignant lesions vary from well differentiated to poorly differentiated with the latter associated with intense mitotic activity, proliferation of neocapillaries, and large areas of hemorrhagic necrosis
• in late stage lesions, small ductular-like cells are found in conjunction with inflammatory cells or scattered among tumor cells and are frequently organized into a duct-like pattern
• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

cellular
• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

Mouse Models of Human Disease
OMIM IDRef(s)
Hepatocellular Carcinoma 114550 J:34434