Phenotypes associated with this allele

• Allele Symbol: Gtf2ird1⁺
• Allele Name: wild type
• Allele ID: MGI:2439610
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Gtf2ird1^Gt(XE465)Byg/Gtf2ird1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3831537
ht2	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+	involves: C57BL/6 * CBA	MGI:3820243
ht3	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+	involves: C57BL/6J * CBA/J	MGI:5461563
cx4	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+ Tg(Alb-E2F1)8Sst/0	involves: C57BL/6 * CBA	MGI:5437646
cx5	Gtf2ird1^Tg(Alb1-Myc)166.8Sst/Gtf2ird1^+ Tg(MtTGFA)42Lmb/0	involves: C57BL/6 * CBA * CD-1	MGI:3820248

Genotype
MGI:3831537

ht1

• Allelic Composition: Gtf2ird1^Gt(XE465)Byg/Gtf2ird1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

Head defects in Gtf2ird1^Gt(XE465)Byg/Gtf2ird1⁺ embryos

craniofacial

abnormal craniofacial morphology ( J:143508 )

• some heterozygous mice displayed craniofacial defects

abnormal frontonasal suture morphology ( J:143508 )

• the frontonasal suture was lacking the degree of interdigitation observed in the control

small cranium ( J:143508 )

• in some heterogygous mice

absent frontal bone ( J:143508 )

• in some heterogygous mice

absent interparietal bone ( J:143508 )

• in some heterogygous mice

absent supraoccipital bone ( J:143508 )

• in some heterogygous mice

absent parietal bone ( J:143508 )

• in some heterogygous mice

domed cranium ( J:143508 )

• in some heterogygous mice

narrow head ( J:143508 )

• some heterozygous embryos at E11.5 and E12.5 shows bitemporal narrowing of head

nervous system

hydrocephaly ( J:143508 )

• in some heterogygous mice

exencephaly ( J:143508 )

• in some heterozygous embryos

growth/size/body

absent frontal bone ( J:143508 )

• in some heterogygous mice

narrow head ( J:143508 )

• some heterozygous embryos at E11.5 and E12.5 shows bitemporal narrowing of head

decreased body size ( J:143508 )

• some heterozygous mice are significantly smaller than their wild-type littermates

postnatal growth retardation ( J:143508 )

• hetrozygotes grew significantly slower than control

pigmentation

belly spot ( J:143508 )

• white patches of variable size on the belly at low frequency

skeleton

abnormal frontonasal suture morphology ( J:143508 )

• the frontonasal suture was lacking the degree of interdigitation observed in the control

small cranium ( J:143508 )

• in some heterogygous mice

absent frontal bone ( J:143508 )

• in some heterogygous mice

absent interparietal bone ( J:143508 )

• in some heterogygous mice

absent supraoccipital bone ( J:143508 )

• in some heterogygous mice

absent parietal bone ( J:143508 )

• in some heterogygous mice

domed cranium ( J:143508 )

• in some heterogygous mice

kyphosis ( J:143508 )

• in some heterogygous mice

integument

belly spot ( J:143508 )

• white patches of variable size on the belly at low frequency

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Williams-Beuren syndrome		DOID:1928	OMIM:194050	J:143508

Genotype
MGI:3820243

ht2

• 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:101128 , J:34434 )

• 23% of mutants develop hepatocellular carcinoma by 12 months of age (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)

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:101128 , J:34434 )

• 23% of mutants develop hepatocellular carcinoma by 12 months of age (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)

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

ht3

• 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

cx4

• 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:3820248

cx5

• 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

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

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 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

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