Phenotypes associated with this allele

• Allele Symbol: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}
• Allele Name: transgene insertion 166.8, Snorri S Thorgeirsson
• Allele ID: MGI:2182322
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^Tg(Alb1-Myc)166.8Sst	involves: C57BL/6 * CBA	MGI:3820200
hm2	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^Tg(Alb1-Myc)166.8Sst	involves: C57BL/6J * CBA/J	MGI:5461561
ht3	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+	involves: C57BL/6 * CBA	MGI:3820243
ht4	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+	involves: C57BL/6J * CBA/J	MGI:5461563
cx5	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+ Tg(Alb-E2F1)8Sst/0	involves: C57BL/6 * CBA	MGI:5437646
cx6	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/0 Tg(MtTGFA)42Lmb/0	involves: C57BL/6 * CBA * CD-1	MGI:3819967
cx7	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+ Tg(MtTGFA)42Lmb/0	involves: C57BL/6 * CBA * CD-1	MGI:3820248

Genotype
MGI:3820200

hm1

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}
• Genetic Background: involves: C57BL/6 * CBA

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

craniofacial

malocclusion ( J:102709 )

• 20% of mice have a misaligned jaw resulting in chronic overgrowth of teeth

periorbital fullness ( J:102709 )

• periorbital fullness is a characteristic of these mice

asymmetric snout ( J:102709 )

• 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

short snout ( J:102709 )

• mice have a characteristically short snout

growth/size/body

malocclusion ( J:102709 )

• 20% of mice have a misaligned jaw resulting in chronic overgrowth of teeth

periorbital fullness ( J:102709 )

• periorbital fullness is a characteristic of these mice

asymmetric snout ( J:102709 )

• 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

short snout ( J:102709 )

• mice have a characteristically short snout

decreased body weight ( J:102709 )

• 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

malocclusion ( J:102709 )

• 20% of mice have a misaligned jaw resulting in chronic overgrowth of teeth

behavior/neurological

abnormal mastication ( J:102709 )

• the 20% of mice with malocclusions are unable to manipulate hard food pellets

limb grasping ( J:102709 )

• mice display an abnormal clasping or kicking behavior upon lifting

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Williams-Beuren syndrome		DOID:1928	OMIM:194050	J:102709

Genotype
MGI:5461561

hm2

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}
• Genetic Background: involves: C57BL/6J * CBA/J

behavior/neurological

abnormal response to new environment ( J:190478 )

• 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

abnormal eating behavior ( J:190478 )

• mutants show a longer latency to eat than wild-type mice (hyponeophagia)

abnormal fear/anxiety-related behavior ( J:190478 )

• 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

increased anxiety-related response ( J:190478 )

• 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

increased response to stress-induced hyperthermia ( J:190478 )

♂ • mutant males exhibit an elevated temperature increase 10 minutes after an initial stressor, indicating stress-induced hyperthermia

increased grooming behavior ( 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

limb grasping ( J:190478 )

impaired coordination ( J:190478 )

• mutants exhibit decreased motor coordination on all three days of training on the rotarod; females show better motor coordination than males

decreased grip strength ( J:190478 )

• 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

abnormal gait ( J:190478 )

♂ • 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

♂ • hindpaws of males show decreased contact area, print area, stand index, intensity, print length, print width, and duty cycle

decreased vertical activity ( J:190478 )

• mutants exhibit decreased number of rearings in a novel environment

abnormal circadian behavior ( J:190478 )

• mutants exhibit decreased circadian activity (less activity during the dark phase); females however, are more active than males

abnormal nest building behavior ( 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/body

periorbital fullness ( J:190478 )

• periorbital fullness

short snout ( J:190478 )

decreased body weight ( J:190478 )

♂ • analyzed only in males

postnatal growth retardation ( J:190478 )

slow postnatal weight gain ( J:190478 )

♂ • analyzed only in males

homeostasis/metabolism

increased response to stress-induced hyperthermia ( J:190478 )

♂ • mutant males exhibit an elevated temperature increase 10 minutes after an initial stressor, indicating stress-induced hyperthermia

increased circulating corticosterone level ( 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

craniofacial

abnormal jaw morphology ( J:190478 )

• about 20% of mutants exhibit a misaligned jaw

periorbital fullness ( J:190478 )

• periorbital fullness

short snout ( J:190478 )

skeleton

abnormal jaw morphology ( J:190478 )

• about 20% of mutants exhibit a misaligned jaw

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Williams-Beuren syndrome		DOID:1928	OMIM:194050	J:190478

Genotype
MGI:3820243

ht3

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1⁺
• Genetic Background: involves: C57BL/6 * CBA

liver/biliary system

increased liver weight ( J:34434 )

• 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

abnormal hepatocyte morphology ( J:34434 )

• 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

increased liver tumor incidence ( J:101128 )

• mutants develop diffuse liver dysplasia by 6-9 months of age

increased hepatocellular carcinoma incidence ( J:34434 , J:101128 )

• 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)

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a slightly higher incidence

neoplasm

increased liver tumor incidence ( J:101128 )

• mutants develop diffuse liver dysplasia by 6-9 months of age

increased hepatocellular carcinoma incidence ( J:34434 , J:101128 )

• 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)

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a slightly higher incidence

growth/size/body

increased liver weight ( J:34434 )

• 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

Genotype
MGI:5461563

ht4

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1⁺
• Genetic Background: involves: C57BL/6J * CBA/J

behavior/neurological

abnormal eating behavior ( J:190478 )

• mutants show a longer latency to eat than wild-type mice (hyponeophagia)

impaired coordination ( J:190478 )

• mutants exhibit decreased motor coordination on the rotarod

abnormal circadian behavior ( J:190478 )

• mutants exhibit decreased circadian activity (less activity during the dark phase)

growth/size/body

decreased body weight ( J:190478 )

♂ • analyzed only in males

postnatal growth retardation ( J:190478 )

slow postnatal weight gain ( J:190478 )

♂ • analyzed only in males

Genotype
MGI:5437646

cx5

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1⁺; Tg(Alb-E2F1)8Sst/0
• Genetic Background: involves: C57BL/6 * CBA

neoplasm

increased liver tumor incidence ( J:101128 )

• mutants develop diffuse liver dysplasia by 3 months of age

increased hepatocellular carcinoma incidence ( J:101128 )

• 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

liver/biliary system

increased liver tumor incidence ( J:101128 )

• mutants develop diffuse liver dysplasia by 3 months of age

increased hepatocellular carcinoma incidence ( J:101128 )

• 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		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:101128 , J:170790

Genotype
MGI:3819967

cx6

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/0; Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * CD-1

neoplasm

increased hepatocellular carcinoma incidence ( J:4527 )

• 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

liver/biliary system

increased hepatocellular carcinoma incidence ( J:4527 )

• 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

Genotype
MGI:3820248

cx7

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1⁺; Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * CD-1

liver/biliary system

increased hepatocyte apoptosis ( J:34434 )

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

multifocal hepatic necrosis ( J:34434 )

• 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

increased liver weight ( J:34434 )

• 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

abnormal hepatocyte morphology ( J:34434 )

• most mice by 2 months of age have extensive dysplastic changes in the liver ranging from moderate cellular pleomorphism and hypertrophy to more advanced polymorphisms 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

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

increased hepatocellular carcinoma incidence ( J:34434 )

• 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

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

neoplasm

increased hepatocellular carcinoma incidence ( J:34434 )

• 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

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

cellular

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

increased hepatocyte apoptosis ( J:34434 )

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

multifocal hepatic necrosis ( J:34434 )

• 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

growth/size/body

increased liver weight ( J:34434 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:34434